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

Proceedings of the National Academy of Sciences of the United States of America
Anna K de RegtRobert T Sauer

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.

References

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Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Nov 6, 2007·Cell·Jungsan SohnRobert T Sauer
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Citations

Dec 26, 2015·Biochimica Et Biophysica Acta·Miroslaw JarzabBarbara Lipinska
Mar 13, 2019·Journal of Bacteriology·Elizabeth M HartThomas J Silhavy
Aug 18, 2020·FEMS Microbiology Reviews·Astra Heywood, Iain L Lamont
Nov 3, 2017·Scientific Reports·Alvaro Cortes CabreraPaula Petrone
May 4, 2015·The Journal of Microbiology·Dong Young Kim
Nov 17, 2020·Frontiers in Molecular Biosciences·Sarah Wettstadt, María A Llamas
Dec 3, 2020·Molecular Plant-microbe Interactions : MPMI·Haibi WangBrian H Kvitko
Apr 15, 2021·Molecular Plant-microbe Interactions : MPMI

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