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The protein stability and chromatin functions of UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) are regulated in a cell-cycle-dependent manner. We report a structural characterization of the complex between UHRF1 and the deubiquitinase USP7. The first two UBL domains of USP7 bind to the polybasic region (PBR) of UHRF1, and this interaction is required for the USP7-mediated deubiquitination of UHRF1. Importantly, we find that the USP7-binding site of the UHRF1 PBR overlaps with the region engaging in an intramolecular interaction with the N-terminal tandem Tudor domain (TTD). We show that the USP7-UHRF1 interaction perturbs the TTD-PBR interaction of UHRF1, thereby shifting the conformation of UHRF1 from a TTD-"occluded" state to a state open for multivalent histone binding. Consistently, introduction of a USP7-interaction-defective mutation to UHRF1 significantly reduces its chromatin association. Together, these results link USP7 interaction to the dynamic deubiquitination and chromatin association of UHRF1.

Fusion of the viral and host cell membranes is a necessary first step for infection by enveloped viruses and is mediated by the envelope glycoprotein. The transmembrane subunits from the structurally defined "class I" glycoproteins adopt an α-helical "trimer-of-hairpins" conformation during the fusion pathway. Here, we present our studies on the envelope glycoprotein transmembrane subunit, GP2, of the CAS virus (CASV). CASV was recently identified from annulated tree boas (Corallus annulatus) with inclusion body disease and is implicated in the disease etiology. We have generated and characterized two protein constructs consisting of the predicted CASV GP2 core domain. The crystal structure of the CASV GP2 post-fusion conformation indicates a trimeric α-helical bundle that is highly similar to those of Ebola virus and Marburg virus GP2 despite CASV genome homology to arenaviruses. Denaturation studies demonstrate that the stability of CASV GP2 is pH dependent with higher stability at lower pH; we propose that this behavior is due to a network of interactions among acidic residues that would destabilize the α-helical bundle under conditions where the side chains are deprotonated. The pH-dependent stability of the post-fusion structure has been observed in Ebola virus and Marburg virus GP2, as well as other viruses that enter via the endosome. Infection experiments with CASV and the related Golden Gate virus support a mechanism of entry that requires endosomal acidification. Our results suggest that, despite being primarily arenavirus like, the transmembrane subunit of CASV is extremely similar to the filoviruses.

We develop theory to explain how CEOs' observable personality traits influence market perceptions of firm risk and shareholder returns. Using a linguistic tool to measure nearly 3,000 CEOs' personality traits, we find that CEOs' observed levels of conscientiousness, neuroticism, and extraversion have important consequences for the perceived riskiness of the firm, as reflected in stock volatility. We also find that these traits alter the relationship between stock risk and returns. Whereas financial economic theory generally posits a positive relationship between risk and returns, on average, we find that this relationship may be either positive or negative for a specific firm depending upon the observed personality of its CEO. Our theory and findings extend upper echelons research by showing that CEOs' personality traits not only affect market perceptions of the firm but also how those perceptions translate into value creation. [ABSTRACT FROM AUTHOR]

This paper explores how executives' prior employment ties to interlocking directors, or those who hold additional board seats or executive positions at outside firms, influence individual executive interfirm mobility. As organizational boundary spanners, interlocking directors may be able to influence executive outcomes both within and outside of executives' current firms. But given natural constraints on internal promotion for executives, we suggest most executives will tend to leverage ties to interlocking directors to access external opportunities, as manifested by movement to outside firms. Analysis of interfirm mobility among a sample of Standard & Poor's 1500 executives between 2000 and 2014 offer support for this idea. We find a positive association between individual executives' prior employment ties to interlocking directors and their hazard of movement to outside firms, including to the other firms where these directors serve. At the same time, we argue and find that the strength of this latter relationship will further depend on directors' competing motivations owing to their specific positions in the focal and interlocking firms. Whereas holding a lead position on the focal firm's board (i.e., as chairperson or lead independent director) weakens this relationship, holding the position of chief executive officer in the interlocking firm strengthens it. Our theory and findings highlight the unique and important role of interlocking directors in executive interfirm mobility and, in doing so, contribute novel insights regarding how ties to boundary spanners can influence individual outcomes for those to whom they are linked. Supplemental Material: The e-companion is available at https://doi.org/10.1287/orsc.2022.1638. [ABSTRACT FROM AUTHOR]

Recent research has pointed to pipelines, or sequenced hiring of individuals from the same source organizations over time, as a common practice employed by firms to reduce labor market imperfections and create human capital resource advantages. We extend this literature by considering how pipelines may emerge not just out of strategic intent but also out of informal social processes reflecting network transitivity and homophily. Using bipartite social network analysis techniques in a sample of 110 public U.S. electronics component manufacturers, we argue and find evidence for transitive effects between firms' employee-based ties to elite educational institutions and the formation of interfirm employee pipelines. We demonstrate that pipelines are more likely to form between firms that both hire educational elites, especially when those firms share ties to the same elite schools and when those shared elite schools are executives' alma mater(s). We also find that these effects tend to be more pronounced when the focal firm has higher growth potential, encouraging mobility by attracting potential elite candidates and facilitating the two-way matching process in labor markets. Our theory and findings contribute to a better understanding of informal processes underlying pipeline formation and specifically demonstrate how hiring tendencies may lead to closed recruiting networks characterized by elite replication. [ABSTRACT FROM AUTHOR]

Strategic entrepreneurship integrates the fields of strategy and entrepreneurship to consider firms' simultaneous engagement in opportunity- and advantage-seeking behaviors to create wealth. Since its conceptualization in the early 2000s, the study of SE has gained considerable momentum. At the same time, some scholars criticize SE and question its comprehensiveness as a way to understand the strategic application of entrepreneurship. We present a comprehensive review and integration of research related to the study of SE as a construct, theoretical model, and research domain. In doing this, we offer a research agenda across these different approaches to the study of SE. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis places an enormous burden on the welfare of humanity. Its ability to grow and its pathogenicity are linked to sulfur metabolism, which is considered a fertile area for the development of antibiotics, particularly because many of the sulfur acquisition steps in the bacterium are not found in the host. Sulfite reduction is one such mycobacterium-specific step and is the central focus of this paper. Sulfite reduction in Mycobacterium smegmatis was investigated using a combination of deletion mutagenesis, metabolite screening, complementation, and enzymoiogy. The initial rate parameters for the purified sulfite reductase from M. tuberculosis were determined under strict anaerobic conditions [[k.sup.cat] = 1.0 ([+ or -] 0.1) electron consumed per second, and [K.sub.m(S[O.sub.3-2] = 27 ([+ or -1]) ptM], and the enzyme exhibits no detectible turnover of nitrite, which need not be the case in the sulfite/nitrite reductase family. Deletion of sulfite reductase (sirA, originally misannotated nirA) reveals that it is essential for growth on sulfate or sulfite as the sole sulfur source and, further, that the nitrite-reducing activities of the cell are incapable of reducing sulfite at a rate sufficient to allow growth. Like their nitrite reductase counterparts, sulfite reductases require a siroheme cofactor for catalysis. Rv2393 (renamed chel) resides in the sulfur reduction operon and is shown for the first time to encode a ferrochelatase, a catalyst that inserts [Fe.sup.2+] into siroheme. Deletion of che1 causes cells to grow slowly on metabolites that require sulfite reductase activity. This slow-growth phenotype was ameliorated by optimizing growth conditions for nitrite assimilation, suggesting that nitrogen and sulfur assimilation overlap at the point of ferrochelatase synthesis and delivery.

Polyubiquitination by E2 and E3 enzymes is crucial to cell cycle control, epigenetic regulation, and development. The hallmark of the E2 family is the ubiquitin (Ub)‐conjugating (UBC) domain that forms a dynamic thioester conjugate with ubiquitin (E2~Ub). Numerous studies have focused on E2 surfaces, such as the N‐terminal and crossover helices, that directly interact with an E3 or the conjugated ubiquitin to stabilize the active, "closed" state of the E2~Ub. However, it remains unclear how other E2 surfaces regulate ubiquitin transfer. Here, we demonstrate the helix–turn–helix (HTH) motif of the UBC tunes the intrinsic polyubiquitination activity through distinct functions in different E2s. Interestingly, the E2HTH motif is repurposed in UBE2S and UBE2R2 to interact with the conjugated or acceptor ubiquitin, respectively, modulating ubiquitin transfer. Furthermore, we propose that Anaphase‐Promoting Complex/Cyclosome binding to the UBE2SHTH reduces the conformational space of the flexible E2~Ub, demonstrating an atypical E3‐dependent activation mechanism. Altogether, we postulate the E2HTH motif evolved to provide new functionalities that can be harnessed by E3s and permits additional regulation to facilitate specific E2‐E3‐mediated polyubiquitination. Synopsis: Ubiquitin (Ub)‐conjugating E2 enzymes control substrate ubiquitination by dictating the linkage specificity of polyubiquitin chains and interacting with E3 ligases via specific surfaces, but the contribution of additional surface regions is unclear. Here, variable ubiquitin interactions of the E2 helix‐turn‐helix (HTH) motif are found to differentially modulate polyubiquitination in diverse E2s. Phylogenetic analysis reveals the HTH motif as a variable region, yet harboring functionally important and conserved charged residues within the distinct E2 family members.Ubiquitin binding to the E2HTH can be repurposed by different E2s, such as cell cycle regulators UBE2R/CDC34 and UBE2S, and tune intrinsic E2 activity.The positively charged UBE2R‐HTH facilitates acceptor ubiquitin recruitment and efficient chain elongation by dictating the dynamics of the gating loop near the enzyme active site.The negatively charged UBE2S‐HTH interacts with the donor Ub, influences the "open" and "closed" states of the UBE2S~Ub conjugate, and enhances ubiquitination by the E3 APC/C by reducing the conformation space of the "open" states. [ABSTRACT FROM AUTHOR]

Research Summary: We introduce an open‐source dataset documenting the reasons for CEO departure in S&P 1500 firms from 2000 through 2018. In our dataset, we code for various forms of voluntary and involuntary departure. We compare our dataset to three published datasets in the CEO succession literature to assess both the qualitative and quantitative differences among them and to explore how these differences impact empirical findings associated with the performance‐CEO dismissal relationship. The dataset includes eight different classifications for CEO turnover, a narrative description of each departure event, and links to sources used in constructing the narrative so that future researchers can validate or adapt the coding. The resulting data are available at (https://doi.org/10.5281/zenodo.4543893). Managerial Summary: This article describes the development of an open‐source database of all CEO dismissals and departures in the S&P 1500 between 2000 and 2018. Prior research on CEO turnover either does not capture the cause of departure or has coded the event independently, leading to inconsistencies and a lack of transparency in coding schemes. This has made it difficult to generate knowledge on the causes and consequences of CEO dismissal. We describe how we developed the database, and we explore how our dataset compares to prior CEO dismissal research. The resulting data are available at (https://doi.org/10.5281/zenodo.4543893). [ABSTRACT FROM AUTHOR]

Comprehensive mutagenesis of the light chain complementarity determining regions (CDRs) of HIV-1 antibody D5 (which binds its target, '5-Helix', with a reported KD of 50 pM). The results for the affinity of D5 for 5-Helix which arises from extended interactions involving both the heavy and light chains of D5 provide significant insight for future antibody engineering efforts.