Staphylococcus aureus FtsZ and PBP4 bind to the conformationally dynamic N-terminal domain of GpsB
- University of South Florida, United States
Abstract
In the Firmicutes phylum, GpsB is a membrane associated protein that coordinates peptidoglycan synthesis with cell growth and division. Although GpsB has been studied in several bacteria, the structure, function, and interactome of Staphylococcus aureus GpsB is largely uncharacterized. To address this knowledge gap, we solved the crystal structure of the N-terminal domain of S. aureus GpsB, which adopts an atypical, asymmetric dimer, and demonstrates major conformational flexibility that can be mapped to a hinge region formed by a three-residue insertion exclusive to Staphylococci. When this three-residue insertion is excised, its thermal stability increases, and the mutant no longer produces a previously reported lethal phenotype when overexpressed in Bacillus subtilis. In S. aureus, we show that these hinge mutants are less functional and speculate that the conformational flexibility imparted by the hinge region may serve as a dynamic switch to finetune the function of the GpsB complex and/or to promote interaction with its various partners. Furthermore, we provide the first biochemical, biophysical, and crystallographic evidence that the N-terminal domain of GpsB binds not only PBP4, but also FtsZ, through a conserved recognition motif located on their C-termini, thus coupling peptidoglycan synthesis to cell division. Taken together, the unique structure of S. aureus GpsB and its direct interaction with FtsZ/PBP4 provide deeper insight into the central role of GpsB in S. aureus cell division.
Data availability
All crystal structures have been deposited in the RCSB Protein Data Bank (PDB) with accession IDs of: Sa GpsB NTD (PDB ID 8E2B), Sa GpsB NTD + Sa PBP4 C-term (PDB ID 8E2C).
Article and author information
Author details
Funding
National Institutes of Health (R21 AI164775)
- Yu Chen
National Institutes of Health (R35 GM133617)
- Prahathees Eswara
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jie Xiao, Johns Hopkins University, United States
Version history
- Preprint posted: October 25, 2022 (view preprint)
- Received: December 14, 2022
- Accepted: April 15, 2024
- Accepted Manuscript published: April 19, 2024 (version 1)
- Version of Record published: May 1, 2024 (version 2)
Copyright
© 2024, Sacco et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Staphylococcus aureus FtsZ and PBP4 bind to the conformationally dynamic N-terminal domain of GpsB
eLife 13:e85579.
https://doi.org/10.7554/eLife.85579
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