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re-refined 1vcw, CRYSTAL STRUCTURE OF DEGS AFTER BACKSOAKING THE ACTIVATING PEPTIDEre-refined 1vcw, CRYSTAL STRUCTURE OF DEGS AFTER BACKSOAKING THE ACTIVATING PEPTIDE
Structural highlights
FunctionDEGS_ECOLI When heat shock or other environmental stresses disrupt protein folding in the periplasm, DegS senses the accumulation of unassembled outer membrane porins (OMPs) and then initiates RseA (anti sigma-E factor) degradation by cleaving it in its periplasmic domain, making it an attractive substrate for subsequent cleavage by RseP. This cascade that ultimately leads to the sigma-E-driven expression of a variety of factors dealing with folding stress in the periplasm and OMP assembly.[1] [2] Publication Abstract from PubMedIn E. coli, outer-membrane stress causes a transcriptional response through a signaling cascade initiated by DegS cleavage of a transmembrane antisigma factor. Each subunit of DegS, an HtrA-family protease, contains a protease domain and a PDZ domain. The trimeric protease domain is autoinhibited by the unliganded PDZ domains. Allosteric activation requires binding of unassembled outer-membrane proteins (OMPs) to the PDZ domains and protein substrate binding. Here, we identify a set of DegS residues that cluster together at subunit-subunit interfaces in the trimer, link the active sites and substrate binding sites, and are crucial for stabilizing the active enzyme conformation in response to OMP signaling. These residues are conserved across the HtrA-protease family, including orthologs linked to human disease, supporting a common mechanism of allosteric activation. Indeed, mutation of residues at homologous positions in the DegP quality-control protease also eliminates allosteric activation. A Conserved Activation Cluster Is Required for Allosteric Communication in HtrA-Family Proteases.,de Regt AK, Kim S, Sohn J, Grant RA, Baker TA, Sauer RT Structure. 2015 Mar 3;23(3):517-26. doi: 10.1016/j.str.2015.01.012. Epub 2015 Feb, 19. PMID:25703375[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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