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We learned that proteins with unique 3D structures can switch folds (referred to as "metamorphic" or shapeshifting proteins), and a new class of proteins, called intrinsically disordered proteins (IDPs), that lack structure but can either transition to order, or in many cases, be functional in the absence of any structure ("fuzzy" logic), was discovered. This paper showed that structured proteins and IDPs could be separated by a straight line on a plot of a protein's net charge ( I Y i -axis) versus its overall hydropathy ( I X i -axis) using the Kyte and Doolittle hydropathy scale. Until the late 1990s, we believed that protein function required a unique, well-defined 3D structure encrypted in the amino acid sequence. This collection is a small token of the respect, admiration, and affection the contributors have for Prof. Vladimir (Volodya) Uversky. [Extracted from the article]

The SARS-CoV-2 nucleocapsid (N) protein is crucial for the highly organized packaging and transcription of the genomic RNA. Studying atomic details of the role of its intrinsically disordered regions (IDRs) in RNA recognition is challenging due to the absence of structure and to the repetitive nature of their primary sequence. IDRs are known to act in concert with the folded domains of N and here we use NMR spectroscopy to identify the priming events of N interacting with a regulatory SARS-CoV-2 RNA element. 13C-detected NMR experiments, acquired simultaneously to 1H detected ones, provide information on the two IDRs flanking the N-terminal RNA binding domain (NTD) within the N-terminal region of the protein (NTR, 1–248). We identify specific tracts of the IDRs that most rapidly sense and engage with RNA, and thus provide an atom-resolved picture of the interplay between the folded and disordered regions of N during RNA interaction. [ABSTRACT FROM AUTHOR]

The current work investigated SARS‐CoV‐2 Nucleocapsid (NCAP or N protein) interactors in A549 human lung cancer cells using a SILAC‐based mass spectrometry approach. NCAP interactors included proteins of the stress granule (SG) machinery and immunoregulators. NCAP showed specific interaction with the SG proteins G3BP1, G3BP2, YTHDF3, USP10 and PKR, and translocated to SGs following oxidative stress and heat shock. Treatment of recombinant NCAP with RNA isolated from A549 cells exposed to oxidative stress‐stimulated NCAP to undergo liquid–liquid phase separation (LLPS). RNA degradation using RNase A treatment completely blocked the LLPS property of NCAP as well as its SG association. The RNA intercalator mitoxantrone also disrupted NCAP assembly in vitro and in cells. This study provides insight into the biological processes and biophysical properties of the SARS‐CoV‐2 NCAP. [ABSTRACT FROM AUTHOR]