6tpi
EnvC bound to the FtsX periplasmic domain
Structural highlights
FunctionENVC_ECOLI Activator of the cell wall hydrolases AmiA and AmiB. Required for septal murein cleavage and daughter cell separation during cell division. In vitro, exhibits weak endoproteolytic activity on beta-casein.[1] [2] [3] [4] Publication Abstract from PubMedFtsEX 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 A 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. Insights into bacterial cell division from a structure of EnvC bound to the FtsX periplasmic domain.,Cook J, Baverstock TC, McAndrew MBL, Stansfeld PJ, Roper DI, Crow A Proc Natl Acad Sci U S A. 2020 Nov 10;117(45):28355-28365. doi: , 10.1073/pnas.2017134117. Epub 2020 Oct 23. PMID:33097670[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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