8wtb
Crystal structure of McsA/McsB complex truncated by chymotrypsin
Structural highlights
FunctionMCSB_BACSU Catalyzes the specific phosphorylation of arginine residues in a large number of proteins. Is part of the bacterial stress response system, where it is involved in regulating the global heat shock repressor CtsR; phosphorylates arginine residues in the winged helix-turn-helix domain of CtsR, thereby preventing its binding to DNA and consequently inducing the expression of repressed genes. The transcriptional repressor HrcA, the chaperone GroEL, the unfoldase ClpC, together with several ribosomal subunits, represent other physiological targets of McsB under stress conditions. Protein arginine phosphorylation has a physiologically important role and is involved in the regulation of many critical cellular processes, such as protein homeostasis, motility, competence, and stringent and stress responses, by regulating gene expression and protein activity. Functions as an adapter whose kinase activity is required for ClpCP-mediated degradation of CtsR during heat stress. Is required for the delocalization of competence proteins from the cell poles, probably via a role in the degradation of anchor proteins.[1] [2] [3] [4] [5] Publication Abstract from PubMedIn gram-positive bacteria, phosphorylated arginine functions as a protein degradation signal in a similar manner as ubiquitin in eukaryotes. The protein-arginine phosphorylation is mediated by the McsAB complex, where McsB possesses kinase activity and McsA modulates McsB activity. Although mcsA and mcsB are regulated within the same operon, the role of McsA in kinase activity has not yet been clarified. In this study, we determined the molecular mechanism by which McsA regulates kinase activity. The crystal structure of the McsAB complex shows that McsA binds to the McsB kinase domain through a second zinc-coordination domain and the subsequent loop region. This binding activates McsB kinase activity by rearranging the catalytic site, preventing McsB self-assembly, and enhancing stoichiometric substrate binding. The first zinc-coordination and coiled-coil domains of McsA further activate McsB by reassembling the McsAB oligomer. These results demonstrate that McsA is the regulatory subunit for the reconstitution of the protein-arginine kinase holoenzyme. This study provides structural insight into how protein-arginine kinase directs the cellular protein degradation system. Structural insights into the regulation of protein-arginine kinase McsB by McsA.,Arifuzzaman M, Kwon E, Kim DY Proc Natl Acad Sci U S A. 2024 Apr 23;121(17):e2320312121. doi: , 10.1073/pnas.2320312121. Epub 2024 Apr 16. PMID:38625935[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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