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In bacteria and archaea, tripartite ATP-independent periplasmic (TRAP) transporters uptake essential nutrients. TRAP transporters receive their substrates via a secreted soluble substrate-binding protein. How a sodium ion-driven secondary active transporter is strictly coupled to a substrate-binding protein is poorly understood. Here we report the cryo-EM structure of the sialic acid TRAP transporter SiaQM from Photobacterium profundum at 2.97 Å resolution. SiaM comprises a “transport” domain and a “scaffold” domain, with the transport domain consisting of helical hairpins as seen in the sodium ion-coupled elevator transporter VcINDY. The SiaQ protein forms intimate contacts with SiaM to extend the size of the scaffold domain, suggesting that TRAP transporters may operate as monomers, rather than the typically observed oligomers for elevator-type transporters. We identify the Na+ and sialic acid binding sites in SiaM and demonstrate a strict dependence on the substrate-binding protein SiaP for uptake. We report the SiaP crystal structure that, together with docking studies, suggest the molecular basis for how sialic acid is delivered to the SiaQM transporter complex. We thus propose a model for substrate transport by TRAP proteins, which we describe herein as an ‘elevator-with-an-operator’ mechanism.

Demands for major antitrust reform are coming from all directions: politicians, industrial organization (IO) economists, and antitrust lawyers. While the political, legal, and economic debates vary in important ways, they all boil down to a single question: Do we need a “New” Sherman Act? Progressive IO economists argue that a “crisis” of competition in markets—evidenced by increasing levels of aggregate industry concentration—has resulted in systematic market power across the economy, and that a crisis of institutional credibility in the courts has biased antitrust law in favor of defendants. However, as this Article illustrates, the economic and empirical evidence support neither proffer. Rather than reform based on upon evidence of market failure or a failure of antitrust institutions, Progressive IO economists call for reform based upon the nirvana fallacy—a comparison of the today’s institutions with an imaginary set of perfect institutions guided by omniscient and well-intending economists. But economics is not on the agenda of current proposals for antitrust reform and calls for a “New” Sherman Act threaten to upend the long-standing partnership between law and economics on which the consumer welfare standard is predicated. Without such a partnership, antitrust institutions will struggle to achieve their objective of promoting competition on behalf of Americans.

In bacteria and archaea, tripartite ATP-independent periplasmic (TRAP) transporters uptake essential carboxylate- and sulfonate-containing nutrients into the cytoplasm. Unlike other secondary active transporters, TRAP transporters cannot receive their substrates directly, but do so indirectly via a secreted soluble substrate-binding protein. How a sodium-driven secondary active transporter is strictly coupled to a passenger-carrying substrate-binding domain is poorly understood. Here, we report the cryo-EM structure of the sialic acid TRAP transporter SiaQM from Photobacterium profundum at 2.97 Å resolution. SiaM has 12-TMs that come together to form a “transport” domain and a “scaffold” domain, with the transport domain consisting of helical hairpins as seen in the sodium-coupled elevator transporter VcINDY. Interestingly, the SiaQ protein forms intimate contacts with SiaM to extend the size of the scaffold domain, indicating TRAP transporters may operate as monomers, rather than the typically observed oligomers. We have identified the Na+ and sialic acid binding sites in SiaM and confirmed a strict dependence on the substrate-binding protein SiaP for uptake. We have determined the SiaP crystal structure that, together with co-evolution driven docking studies, provides a molecular basis for how sialic acid is delivered to the SiaQM transporter complex. We conclude that TRAP proteins are conceptually a marriage between an ABC importer and a secondary active transporter, which we describe herein as an ‘elevator-with-an-operator’ mechanism.

Some scholars claim that identifying with religious groups leads to a greater inclination toward violence than identifying with secular groups and we test this proposition in a unique experimental ...

Judge Koh handed down a sweeping opinion in May 2019 condemning as antitrust violations many of Qualcomm’s business practices related to the royalty rates it charged to license its SEPs. The district court opinion significantly expands the scope of liability for refusals to deal and for non-predatory pricing behavior, further eroding the longstanding symmetrical approach to antitrust enforcement regardless of the kind of property involved. We find three glaring errors in the district court opinion. First, the court expands the exception to the general rule permitting refusals to deal, as laid out in Aspen Skiing, well beyond the outer boundary of Section 2 by applying it to contracts negotiated by Qualcomm over 20 years ago and by inferring the company was willing to sacrifice profits even in the face of evidence that the change in dealing was implemented to increase short-term profits. Second, the district court accepted a price squeeze theory—characterized by the FTC as a “tax” on OEMs transacting with Qualcomm’s rivals—directly contrary to the Supreme Court’s holding in linkLine. Third, the court erroneously concluded that Qualcomm’s exclusive dealing arrangements with Apple violate the Sherman Act, despite a glaring failure by the FTC to prove substantial foreclosure, contrary to modern antitrust precedent and economic theory, both of which make crystal clear that proof of substantial foreclosure is necessary to showing an anticompetitive effect from exclusive dealing. The district court’s inappropriate extension of antitrust liability in three separate areas of well-settled antitrust doctrine is remarkable and threatens to upend important precedent that has successfully guided business conduct for years. Further, the remedy—aside from putting the nation’s security at risk and potentially undermining U.S. leadership in 5G technology and standard-setting—transforms the role of antitrust courts from adjudicators to central planners, a role for which the Trinko Court expressly stated they are ill suited. The decision invites plaintiffs to use the Sherman Act to reach conduct that has been generally shielded from antitrust liability. That invitation is ill advised and should be rejected by the Ninth Circuit, and if necessary, the Supreme Court.

Multicomponent transporters are used by bacteria to transport a wide range of nutrients. These systems use a substrate-binding protein to bind the nutrient with high affinity and then deliver it to a membrane-bound transporter for uptake. Nutrient uptake pathways are linked to the colonisation potential and pathogenicity of bacteria in humans and may be candidates for antimicrobial targeting. Here we review current research into bacterial multicomponent transport systems, with an emphasis on the interaction at the membrane, as well as new perspectives on the role of lipids and higher oligomers in these complex systems.

Multisided platforms have distinct and critical features that set them apart from single-sided markets. This realization has led to a split among courts, antitrust practitioners, and economists as to the best method to assess whether mergers or conduct that involve platforms result in the creation or maintenance of monopoly power and violate the antitrust laws. Some argue that each side of a platform constitutes a separate relevant product market. Others argue for a single, integrated market that incorporates all sides. We argue that any prima facie antitrust assessment of competitive harm must incorporate the impact to consumers on all sides regardless of market definition. We also explain why output effects should be the primary emphasis of competitive effects analyses. The Supreme Court recently and correctly adopted this approach in Ohio v. American Express.

We examined environmental activist behaviour as a function of two different forms of environmental identity: identification with nature (i.e., seeing oneself as part of nature, more often referred to as connectedness to nature) and politicized environmental identity (i.e., seeing oneself as a part of a collective struggle to protect the environment). We extend prior work that found politicized environmental identity mediates a relationship between identification with nature and self-reports of environmental activism (Schmitt, Mackay, et al., 2019) by using observed behavioural indicators of environmental activism: taking pro-environmental buttons (Study 1), donating to an environmental organization (Study 2), or writing pro-environmental letters to politicians (Study 3). In Study 2 the relationship between identification with nature and activist behaviour was fully mediated by politicized environmental identity. In Studies 1 and 3, politicized environmental identity partially mediated a relationship between identification with nature and observed activist behaviour. We estimated the mean effect size of the mediation pathways in all three studies using meta-analysis, which supported the mediation model.

President Trump’s Executive Order on Preventing Online Censorship is the latest in a series of proposals aimed at independent agencies, chiefly the Federal Communications Commission (FCC) and Federal Trade Commission (FTC), that seek to police how tech companies operate their social media platforms. These measures suffer from fatal defects. They run against the weight of First Amendment law and, our focus, beyond the limits of FTC Section 5 authority. We briefly summarize the scope of that authority before analyzing the Executive Order against the backdrop of the First Amendment and Section 5; concluding it would be illegal and imprudent to enforce. We conclude with suggestions for how the FTC should handle the position it finds itself in—facing an Executive Order to consider and study unlawful enforcement actions that not only undermine its independence, but also shift its attention away from its primary mission of consumer protection toward policing free speech.

In the last couple of years, the United States Department of Justice (“DOJ”) and several European countries have reversed previous interventionist decisions and limited the role of antitrust in the resolution of disputes concerning Standard Essential Patent (“SEPs”). These jurisdictions recognize the need to protect intellectual property rights (“IPRs”) by making available injunctions against infringers. Courts have realized that hold-up by a patent holder demanding excessive royalties is not a widespread problem and that patent implementers may hold-out against paying any royalties whilst they continue to practice a patent. They have accordingly adopted new standards for granting injunctions in disputes involving SEPs with the goal of increasing efficiency and legal certainty. We discuss this shift and its implications for competition policy and innovation.

The rise of large firms in the digital economy, including Amazon, Apple, Facebook, and Google, has rekindled the debate about monopolization law. There are proposals to make finding liability easier against alleged digital monopolists by relaxing substantive standards; to flip burdens of proof; and to overturn broad swaths of existing Supreme Court precedent, and even to condemn a law review article. Frank Easterbrook’s seminal 1984 article, The Limits of Antitrust, theorizes that Type I error costs are greater than Type II error costs in the antitrust context, a proposition that has been woven deeply into antitrust law by the Supreme Court. We consider the implications of this assumption on the standard of proof. We find that, taking variants of the Easterbrook assumption as given, the optimal standard of proof is stronger than the preponderance of the evidence standard. Our conclusion is robust to how one specifies the preponderance of the evidence standard and stands in stark contrast to contemporary proposals to reduce or eliminate the burden of proof facing antitrust plaintiffs in digital markets.

Modern antitrust laws (including the federal antitrust laws and the antitrust laws of other states, as well as the cognate laws of numerous other jurisdictions around the world) generally include provisions that limit unilateral business conduct that may create, protect, or extend monopoly power by unreasonably exclusionary practices. In contrast, New York’s main antitrust law, the Donnelley Act of 1899, contains no such provision. The GAI recognizes that adding such a provision to the Donnelley Act is an intended objective of S.933. There are several serious questions, however, raised by key aspects of S.933. Specifically, while S.933 §3 adopts a prohibition on monopolization similar to that found in Section 2 of the Sherman Act, 15 USC § 2, it also includes a prohibition on “abuse of dominance.” S.933 provides limited information regarding the definitions of “dominance” and “abuse.” Rather, S.933 delegates very broad discretion to define these terms to the New York Attorney General (subject to a specific form of legislative veto). This approach presents a number of serious risks and uncertainties. For reasons explained more fully below, the Committee should consider withholding any favorable recommendation on S.933 so long as it contains the abuse-of-dominance provision.

We extend social identity models of pro-environmental collective action by expanding on the plausible role of access to cognitive alternatives to the environmental status quo (i.e., the ability of people to imagine what a sustainable relationship with nature would look like). Using a representative Canadian survey on age, gender, and ethnicity (N = 1029) we evaluate the associations between access to environmental cognitive alternatives and politicized environmental identity and willingness to engage in pro-environmental activist behavior. Additionally, we extend research using exclusively self-reported outcomes by giving participants the opportunity to write and sign a pro-environmental letter to the Canadian Minister of the Environment and Climate Change. Our results suggest that envisioning specific ways in which the status quo can be changed is associated with stronger politicized environmental identity, greater willingness to engage in pro-environmental activist behavior, and increased likelihood of writing and signing a pro-environmental letter to the Canadian Minister of the Environment and Climate Change. All methods and analyses follow our preregistration (https://osf.io/b56ry) and all materials and data are openly available (https://osf.io/24yeq/).

We test common sense psychology of intragroup relations whereby people assume that intragroup respect and ingroup prototypicality are positively related. In Study 1a, participants rated a group member as more prototypical if they learned that group member was highly respected rather than disrespected. In Study 1b, participants rated a group member as more respected by other group members if they learned that group member was prototypical rather than unprototypical. As a commonsense psychology of groups, we reasoned that the perceived relationship between prototypicality and intragroup respect would be stronger for cohesive groups compared to incohesive groups. The effect of intragroup respect on perceptions of prototypicality (Study 2a & 2c) and the effect of prototypicality on perceptions of intragroup respect (Study 2b) were generally stronger for participants considering cohesive groups relative to incohesive groups. However, the interaction effect of prototypicality and group cohesion on intragroup respect did fail to replicate in Study 2d. In Studies 3, 4a, and 4b we manipulated the relationship between prototypicality and intragroup respect and found that when these variables were in perceptual harmony participants perceived groups as more cohesive. The results of eight out of nine studies conducted are consistent with the prediction that people make inferences about intragroup respect, prototypicality, and group cohesion in a manner that maintains perceptual harmony.

Exemptions and immunities limit the reach of the antitrust laws. If the courts and agencies implement exemptions and immunities too expansively, anticompetitive conduct will elude enforcement and thereby injure consumers. The dynamic nature of the digital economy amplifies these concerns. Policymakers, courts, and regulators must diligently assess the ever-changing digital landscape and tailor antitrust doctrine accordingly.

Antitrust institutions in the United States and around the world are at a crossroads. Until now, antitrust has been based upon the consumer welfare standard, which has served as the lodestar of modern antitrust for the past 40 years. The hallmark of modern antitrust enforcement has been a case-by-case approach, driven by economic analysis and an evaluation of conduct on the merits. Courts and competition agencies have generally rejected invitations to jettison this successful approach in favor of presumptions of illegality and other shortcuts. The reason is simple: Relying upon presumptions instead of evidence risks rendering unlawful business behavior that in fact benefits consumers. But there is increasingly talk of a revolution that would overthrow the antitrust regime in the United States and, indeed, around the world. The drumbeat for this revolution appears to be strong and growing, with a broad range of enthusiastic participants and followers, including legal academics and economists, public intellectuals, think tankers, prominent members of Congress, and some foreign competition authorities. The would-be revolution has already had some success—at least as measured by the increasing discussion in academia, the popular press, and social media, and having embedded some of its central ideas in the platforms of both major U.S. political parties. Signs of the gathering revolution can also be seen in the various reports on antitrust and the digital economy emanating from around the world, such as those of the Stigler Center at the University of Chicago, the Australian Competition and Consumer Commission, The United Kingdom’s Competition and Markets Authority, the European Commission’s Directorate-General for Competition, the House Judiciary Committee’s Subcommittee on Antitrust, Commercial, and Administrative Law, and other think tanks and governmental bodies. The more radical revolutionaries want an antitrust regime to address a myriad of perceived socio-political problems, including, but not limited to, income inequality, relative wage depression, and the concentration of political power. Some call for incorporating other forms of regulation—particularly regulation of data and privacy—into the antitrust laws and putting them in the hands of the antitrust regulators. Their revolutionary zeal is aimed generally at the digital economy and in particular at large tech firms. Their proposed “fixes” targeting the largest tech firms run the gamut from the reinvigoration of competition rulemaking at the Federal Trade Commission, to shifting the burden of proof from plaintiffs to defendants in antitrust litigation, to extending the reach of antitrust to content moderation decisions, to size-based presumptions akin to the antitrust approach of the 1960s, to creating a new agency with unlimited regulatory power. These proposals have been refined to the point that they are now ripe, in our view, for rigorous examination from an evidence-based perspective.

Bargaining is all around us. Bargaining is how prices are set across a range of economic activities such as between licensors and licensees of intellectual property, employees and employers, content providers and distributors, health insurers and hospitals, and in many intermediate product markets. Recently, bargaining has played a central role in a number of high-profile antitrust matters. In 2018, the U.S. Department of Justice challenged AT&T’s acquisition of Time Warner — largely on the basis of a bargaining model. Also, in 2018, the U.S. Federal Trade Commission argued that Qualcomm’s market position in cellular chipsets allowed it to leverage higher royalty rates for its standard essential patents (“SEPs”), in violation of its commitment to license its SEPs on fair, reasonable, and non-discriminatory (“FRAND”) terms. In this article, we assess the value of economic bargaining models to predict outcomes for both horizontal and vertical mergers and for unilateral conduct. To that end, we first provide an overview of the economics of bargaining models and their primary features, including the vertical GUPPI variant. We then discuss these models in the context of recent antitrust cases and detail the uneven judicial adoption of bargaining models. Next, we examine whether the current judicial reticence is justified. We review a body of emerging scholarship that suggest some caution on the use of methodologies to predict harm based on bargaining models. This suggests that a healthy degree of judicial skepticism is warranted — whether coherently articulated in opinions or not. In conclusion, we offer some policy recommendations for the use of bargaining models, which we believe will lead to a more balanced approach regarding their use in antitrust matters.

Using ex-ante regulation to replace inefficient and ineffective ex-post litigation based antitrust is a familiar refrain for those interested in regulating large technology firms. But the narrative that antitrust is either solely or predominantly based on ex-post litigation is a false narrative, as both the current antitrust laws and its institutions incorporate many of the features that reformers put forth as ex-ante regulation. As a matter of optimal regulatory design, this is not surprising, as a true ex-ante approach will incorporate both approaches. In the U.S., the Supreme Court has expanded its implied immunity and related common law limits on the use of the antitrust laws in response to the potential costs of inconsistent and overlapping regulation. This forces an ex-ante choice between antitrust and sector specific regulation when addressing specific problems associated with regulated industries. We suggest the ex-ante choice between antitrust and sector regulation be made based on the comparative institutional advantage of each approach, and that such an approach will result in the allocation of duties to deal and price setting to sector specific regulators. Because both approaches are imperfect vehicles for controlling competition, both the initial allocation between antitrust and regulation and the choice to regulate in the first place should be undertaken with caution, and expected to involve a long, slow, and costly evolution towards a more efficient system of antitrust and regulation.

The extraordinary success of the digital sector of the domestic economy is indisputable. With this level of market success, growth, and influence, both economically and culturally, it is perhaps inevitable that these businesses are increasingly at the forefront of public policy discussions. Most relevant for our purposes are the now-common claims that these firms have systematically engaged in anticompetitive conduct, or are otherwise insulated from competitive forces, and that digital platforms’ exercise of monopoly power has remained unchecked at least in part due to gaps in our antitrust laws or lax enforcement of existing laws. This testimony provides insights on three important questions concerning the state of competition in the digital marketplace: (1) Are existing antitrust laws that prohibit monopolization and monopolistic conduct adequate for digital platforms?; (2) Are existing laws adequate to prohibit anticompetitive transactions including for vertical and conglomerate mergers, serial acquisitions, data acquisitions, or acquisitions of potential competitors?; and (3) Is the institutional structure of antitrust enforcement — including the current levels of appropriations to the antitrust agencies, existing agency authorities, congressional oversight of enforcement, and current statutes and case law — adequate to promote the robust enforcement of the antitrust laws?

This comment is submitted by the Global Antitrust Institute (GAI) at Scalia Law School, George Mason University to the Federal Ministry of Economic Affairs and Energy (Bundesministeriums fur Wirtschaft und Energie, hereinafter “BMWi”) for consideration in relation to its proposed amendment to German competition law, the GWB Digitalization Act. The GAI Competition Advocacy Program provides recommendations to facilitate adoption of economically sound competition rules and policies. This comment identifies a number of elements contained in the proposed legislation that have the potential to introduce departures from sound economic analysis into German competition-law enforcement. These include novel provisions affecting the definition of “dominance” and “abuse of dominance,” as well as provisions promoting the use of so-called mandatory access remedies in cases involving digital platforms.

This comment is submitted by the Global Antitrust Institute (GAI) to the European Commission (Commission) for consideration in relation to its consultation on its Notice on the definition of relevant market for the purposes of community competition law.

This comment is submitted by the Global Antitrust Institute (GAI) at the Antonin Scalia Law School, George Mason University to the Federal Trade Commission (FTC) in relation to its proposed examination of whether there is “a sufficient legal basis and empirical economic support” to promulgate a Commission rule that would restrict the use of non-compete clauses in employer-employee contracts.

Migrant workers are beneficial and important factors for the economy where as their life is full of scarce, vulnerable and exploitation. In Globalization, profit motive capitalism emerged through which overuse of resources and worker exploitation occurs. For maintaining dignity and reducing the exploitation over labours government intervention took place by introducing labour laws. But due to the upcoming scenario Covid-19 pandemic affects the economy. Production becomes stagnant. So to maintain the pace of the economy the government has removed various labour laws which may affect the life of migrant labourers. Definitely it has seen the economy is somehow dependent on labourers. But now the economy is going to be stable at the cost of migrant workers. This study is an attempt to analyse the extent of labour laws followed in the grassroot level before lockdown and in which way it has increased after lockdown and unlock condition.

Author(s): Barnett, Jonathan; Baye, Michael R; Cooper, James C; Crane, Daniel A; Elzinga, Kenneth G; Epstein, Richard; Garza, Deborah; Hazlett, Thomas W; Hurwitz, Justin Gus; Klein, Benjamin; Klick, Jonathan; Lambert, Thomas A; Lipsky, Tad; Manne, Geoffrey A; Masten, Scott E; Ohlhausen, Maureen; Rill, James; Rybnicek, Jan; Smith, Vernon L; Teece, David; Willig, Robert; Wright, Joshua D; Yun, John M

This comment is submitted by the Global Antitrust Institute (GAI) at the Antonin Scalia Law School, George Mason University to the Federal Trade Commission and Department of Justice regarding the draft 2020 Vertical Merger Guidelines. The GAI Competition Advocacy Program provides a wide range of recommendations to facilitate adoption of economically sound competition policies.

The division of psychotic symptoms into positive and negative categories has largely divided the research on them. While the research on positive symptoms of psychosis has rapidly developed over the last three decades, the literature on negative symptoms has noticeably lagged behind. Negative symptoms have likely been ignored in the treatment literature because they were previously thought to remit following the treatment of positive symptoms. Recent evidence does not consistently support this theory and indicates that the different manifestations of negative symptoms require distinct approaches to treatment. The current review provides a re-evaluation of the theoretical literature on negative symptoms to inform and identify “treatment targets” to reduce them. The “treatment targets” are then translated into intervention strategies using a cognitive behavioral framework. A review of the empirical literature on cognitive behavior therapy for treating negative symptoms is then offered along with a critical discussion of where cognitive behavior therapy stands compared to other interventions and what research is still needed.

We had 354 Americans rate the personalities of Donald Trump and Hillary Clinton. We compared ratings of Trump voters, Clinton voters, and a politically moderate subsample to the left-wing experts' ratings reported in Nai and Maier (2018). We examined the association between raters' reported political orientation and personality ratings of both candidates. We found strong correlations between political orientation of the rater and ratings of the personalities of both Trump and Clinton. We also found that the sample of experts reported in Nai and Maier (2018) rated Trump lower in conscientiousness and agreeableness than our Clinton voters did. These experts also rated Trump lower in conscientiousness, agreeableness, and emotional stability than our politically moderate raters. Our findings show that political preference is strongly associated with the personality ratings of candidates among both expert and non-expert raters.

Henry G. Manne, our friend, Mentor, and colleague, was a pioneer in the economic analysis of law. By consistently challenging the notion that existing institutions were well understood, he expanded the domain of economics to new and fertile ground. In that spirit, our goal in this article is to bring out of the shadows an institution that has thus far evaded the light of economic analysis: antitrust consents. In our view, competition authorities around the world should be asking themselves what ratio of litigation to settlement is optimal for their agency. Over the last 35 years, the United States Federal Trade Commission and the Antitrust Division of the Department of Justice have shifted dramatically toward greater reliance upon consent decrees than upon litigation to resolve antitrust disputes. As an aid to national competition agencies considering the desirability of adopting a similar approach, we focus upon the importance of economic analysis in evaluating movement along the continuum from a law enforcement model to a regulatory model of agency behavior. We draw upon the U.S. experience to substantiate our claim that the costs associated with a shift toward the regulatory model, including the potential distortion in the development of substantive antitrust doctrine, may be under-appreciated and discernable only in the long run. We acknowledge that consent decrees can and should be an important tool in an antitrust agency’s toolkit for resolving antitrust disputes. We contend, however, that a full economic analysis of reliance primarily upon consent decrees is necessary to inform each competition agency’s strategic decision about the optimal mix of law enforcement and regulatory techniques.

Attachment of ubiquitin to proteins relies on a sophisticated enzyme cascade that is tightly regulated. The machinery of ubiquitylation responds to a range of signals, which remarkably includes ubiquitin itself. Thus, ubiquitin is not only the central player in the ubiquitylation cascade but also a key regulator. The ubiquitin E3 ligases provide specificity to the cascade and often bind the substrate, while the ubiquitin-conjugating enzymes (E2s) have a pivotal role in determining chain linkage and length. Interaction of ubiquitin with the E2 is important for activity, but the weak nature of these contacts has made them hard to identify and study. By reviewing available crystal structures, we identify putative ubiquitin binding sites on E2s, which may enhance E2 processivity and the assembly of chains of a defined linkage. The implications of these new sites are discussed in the context of known E2–ubiquitin interactions.