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Insights into intrinsic resistance and bacterial cell division from a structure of EnvC bound to the FtsX periplasmic domain
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Cook, Jonathan P., Baverstock, Tyler, McAndrew, Martin B. L., Stansfeld, Phillip J., Roper, David I. and Crow, Allister (2020) Insights into intrinsic resistance and bacterial cell division from a structure of EnvC bound to the FtsX periplasmic domain. Proceedings of the National Academy of Sciences of the United States of America, 117 (45). pp. 28355-28365. doi:10.1073/pnas.2017134117 ISSN 0027-8424.
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Official URL: https://doi.org/10.1073/pnas.2017134117
Abstract
FtsEX is a bacterial ABC transporter that regulates the activity of periplasmic peptidoglycan amidases via its interaction with the murein hydrolase activator, EnvC. In Escherichia coli, FtsEX is required to separate daughter cells after cell division and for viability in low-osmolarity media. Both the ATPase activity of FtsEX and its periplasmic interaction with EnvC are required for amidase activation, but the process itself is poorly understood. Here we present the 2.1 Å structure of the FtsX periplasmic domain in complex with its periplasmic partner, EnvC. The EnvC-FtsX periplasmic domain complex has a 1-to-2 stoichiometry with two distinct FtsX-binding sites located within an antiparallel coiled coil domain of EnvC. Residues involved in amidase activation map to a previously identified groove in the EnvC LytM domain that is here found to be occluded by a “restraining arm” suggesting a self-inhibition mechanism. Mutational analysis, combined with bacterial two-hybrid screens and in vivo functional assays, verifies the FtsEX residues required for EnvC binding and experimentally test a proposed mechanism for amidase activation. We also define a predicted link between FtsEX and integrity of the outer membrane. Both the ATPase activity of FtsEX and its periplasmic interaction with EnvC are required for resistance to membrane-attacking antibiotics and detergents to which E. coli would usually be considered intrinsically resistant. These structural and functional data provide compelling mechanistic insight into FtsEX-mediated regulation of EnvC and its downstream control of periplasmic peptidoglycan amidases.
Item Type: | Journal Article | |||||||||||||||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | Proceedings of the National Academy of Sciences of the United States of America | |||||||||||||||||||||
Publisher: | National Academy of Sciences | |||||||||||||||||||||
ISSN: | 0027-8424 | |||||||||||||||||||||
Official Date: | November 2020 | |||||||||||||||||||||
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Volume: | 117 | |||||||||||||||||||||
Number: | 45 | |||||||||||||||||||||
Number of Pages: | 11 | |||||||||||||||||||||
Page Range: | pp. 28355-28365 | |||||||||||||||||||||
DOI: | 10.1073/pnas.2017134117 | |||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||||||||
Date of first compliant deposit: | 30 September 2020 | |||||||||||||||||||||
Date of first compliant Open Access: | 27 October 2020 | |||||||||||||||||||||
RIOXX Funder/Project Grant: |
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