Genetic analysis of the septal peptidoglycan synthase FtsWI complex supports a conserved activation mechanism for SEDS-bPBP complexes

Autoři: Ying Li aff001;  Han Gong aff001;  Rui Zhan aff001;  Shushan Ouyang aff001;  Kyung-Tae Park aff002;  Joe Lutkenhaus aff002;  Shishen Du aff001
Působiště autorů: Department of Microbiology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, HB, China aff001;  Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS, United States of America aff002
Vyšlo v časopise: Genetic analysis of the septal peptidoglycan synthase FtsWI complex supports a conserved activation mechanism for SEDS-bPBP complexes. PLoS Genet 17(4): e1009366. doi:10.1371/journal.pgen.1009366
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009366


SEDS family peptidoglycan (PG) glycosyltransferases, RodA and FtsW, require their cognate transpeptidases PBP2 and FtsI (class B penicillin binding proteins) to synthesize PG along the cell cylinder and at the septum, respectively. The activities of these SEDS-bPBPs complexes are tightly regulated to ensure proper cell elongation and division. In Escherichia coli FtsN switches FtsA and FtsQLB to the active forms that synergize to stimulate FtsWI, but the exact mechanism is not well understood. Previously, we isolated an activation mutation in ftsW (M269I) that allows cell division with reduced FtsN function. To try to understand the basis for activation we isolated additional substitutions at this position and found that only the original substitution produced an active mutant whereas drastic changes resulted in an inactive mutant. In another approach we isolated suppressors of an inactive FtsL mutant and obtained FtsWE289G and FtsIK211I and found they bypassed FtsN. Epistatic analysis of these mutations and others confirmed that the FtsN-triggered activation signal goes from FtsQLB to FtsI to FtsW. Mapping these mutations, as well as others affecting the activity of FtsWI, on the RodA-PBP2 structure revealed they are located at the interaction interface between the extracellular loop 4 (ECL4) of FtsW and the pedestal domain of FtsI (PBP3). This supports a model in which the interaction between the ECL4 of SEDS proteins and the pedestal domain of their cognate bPBPs plays a critical role in the activation mechanism.

Klíčová slova:

Antibiotics – Arabinose – Cell cycle and cell division – Hyperexpression techniques – Library screening – Protein interactions – Signaling cascades – Substitution mutation


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