| Structural highlights
Function
DEGS_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 PubMed
In 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
- ↑ Alba BM, Leeds JA, Onufryk C, Lu CZ, Gross CA. DegS and YaeL participate sequentially in the cleavage of RseA to activate the sigma(E)-dependent extracytoplasmic stress response. Genes Dev. 2002 Aug 15;16(16):2156-68. PMID:12183369 doi:10.1101/gad.1008902
- ↑ Meltzer M, Hasenbein S, Mamant N, Merdanovic M, Poepsel S, Hauske P, Kaiser M, Huber R, Krojer T, Clausen T, Ehrmann M. Structure, function and regulation of the conserved serine proteases DegP and DegS of Escherichia coli. Res Microbiol. 2009 Nov;160(9):660-6. doi: 10.1016/j.resmic.2009.07.012. Epub, 2009 Aug 18. PMID:19695325 doi:10.1016/j.resmic.2009.07.012
- ↑ de Regt AK, Kim S, Sohn J, Grant RA, Baker TA, Sauer RT. A conserved activation cluster is required for allosteric communication in HtrA-family proteases. Structure. 2015 Mar 3;23(3):517-526. PMID:25703375 doi:10.1016/j.str.2015.01.012
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