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Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3326-31. doi: 10.1073/pnas.1502372112. Epub 2015 Mar 2.

Steric clashes with bound OMP peptides activate the DegS stress-response protease.

Author information

1
Department of Biology and.
2
Department of Biology and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139.
3
Department of Biology and bobsauer@mit.edu.

Abstract

Escherichia coli senses envelope stress using a signaling cascade initiated when DegS cleaves a transmembrane inhibitor of a transcriptional activator for response genes. Each subunit of the DegS trimer contains a protease domain and a PDZ domain. During stress, unassembled outer-membrane proteins (OMPs) accumulate in the periplasm and their C-terminal peptides activate DegS by binding to its PDZ domains. In the absence of stress, autoinhibitory interactions, mediated by the L3 loop, stabilize inactive DegS, but it is not known how this autoinhibition is reversed during activation. Here, we show that OMP peptides initiate a steric clash between the PDZ domain and the L3 loop that results in a structural rearrangement of the loop and breaking of autoinhibitory interactions. Many different L3-loop sequences are compatible with activation but those that relieve the steric clash reduce OMP activation dramatically. Our results provide a compelling molecular mechanism for allosteric activation of DegS by OMP-peptide binding.

KEYWORDS:

allosteric regulation; outer-membrane proteins; regulated intracellular proteolysis; stress sensor

PMID:
25733864
PMCID:
PMC4371955
DOI:
10.1073/pnas.1502372112
[Indexed for MEDLINE]
Free PMC Article

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