The bacterial actin-like cell division protein FtsA forms antiparallel double filaments upon binding of FtsN

Cell division is essential for the propagation of all living organisms. In the vast majority of bacteria, cell division is carried out by the divisome, a multiprotein machine spanning the cell envelope. The divisome performs membrane invagination, peptidoglycan synthesis and remodelling, and eventually cell separation. Filaments of the tubulin homologue FtsZ form the scaffold for divisome assembly in the cytoplasm, the Z ring. Actin like FtsA tethers FtsZ to the inner membrane and facilitates recruitment of downstream divisome components. The late divisome component FtsN is a bitopic membrane protein that activates peptidoglycan synthesis. Recent genetic studies have suggested that the interaction of FtsA and FtsN is crucial for divisome integrity and function. So far biochemical and structural evidence for the FtsA-FtsN interaction have remained scarce or absent, and we have no mechanistic understanding of its putative signalling function. In this study, I show that Escherichia coli FtsA, upon binding the short, cytoplasmic part of FtsN, forms antiparallel double filaments on lipid monolayers. My complementary X ray crystallography studies provide a near atomic resolution structure of the FtsA double filament and a first insight into the putative FtsA FtsN binding site. FtsA filaments resemble the antiparallel double filaments formed by the actin homologue MreB involved in cell elongation. MreB filaments sense curvature and serve as a rudder in the cell elongation complex, ensuring oriented insertion of peptidoglycan around the cell circumference. Following from that I propose that curvature sensing is conserved in FtsA double filaments and, together with treadmilling FtsZ filaments, provides a guiding mechanism for membrane constriction and septal peptidoglycan synthesis during cell division.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2020

Author dc:creator

• Nierhaus, Tim

Advisor dc:contributor.advisor

• Löwe, Jan

• Cell division
• Divisome
• FtsA
• FtsN
• Artubulin
• X-ray crystallography

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/76c1bec0-a48e-4da6-89b0-a2b284601a1a/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

Author Identifier

0000-0001-5480-8484

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/314707