RT Journal Article
SR Electronic
T1 <em>Staphylococcus aureus</em> FtsZ and PBP4 bind to the conformationally dynamic N-terminal domain of GpsB
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.10.25.513704
DO 10.1101/2022.10.25.513704
A1 Sacco, Michael D.
A1 Hammond, Lauren R.
A1 Noor, Radwan E.
A1 Bhattacharya, Dipanwita
A1 Madsen, Jesper J.
A1 Zhang, Xiujun
A1 Butler, Shane G.
A1 Kemp, M. Trent
A1 Jaskolka-Brown, Aiden C.
A1 Khan, Sebastian J.
A1 Gelis, Ioannis
A1 Eswara, Prahathees J.
A1 Chen, Yu
YR 2022
UL http://biorxiv.org/content/early/2022/10/25/2022.10.25.513704.abstract
AB Bacterial cell division is a tightly regulated process that requires the formation of a dynamic multi-protein complex. In the Firmicutes phylum, GpsB is a membrane associated protein that coordinates peptidoglycan synthesis for cell growth and division. Although GpsB has been studied in several organisms, the structure, function, and interactome of Staphylococcus aureus GpsB is largely uncharacterized, despite being reported as uniquely essential for growth in this clinically relevant bacterium. To address this knowledge gap, we solved the crystal structure of the N-terminal domain of S. aureus GpsB. This structure reveals an atypical asymmetric dimer, and 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. 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-terminus, thus linking peptidoglycan synthesis with 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.Competing Interest StatementThe authors have declared no competing interest.