Show simple item record

dc.contributor.authorNierhaus, Tim
dc.date.accessioned2020-12-04T13:59:57Z
dc.date.available2020-12-04T13:59:57Z
dc.date.submitted2020-06-01
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/314707
dc.description.abstractCell 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.
dc.description.sponsorshipBoehringer Ingelheim Fonds PhD fellowship (Honorary) Vice-Chancellor's Award, Cambridge Commonwealth, European & International Trust MRC studentship
dc.rightsAll Rights Reserved
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/
dc.subjectCell division
dc.subjectDivisome
dc.subjectFtsA
dc.subjectFtsN
dc.subjectArtubulin
dc.subjectX-ray crystallography
dc.titleThe bacterial actin-like cell division protein FtsA forms antiparallel double filaments upon binding of FtsN
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridge
dc.identifier.doi10.17863/CAM.61813
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved/
dc.contributor.orcidNierhaus, Tim [0000-0001-5480-8484]
rioxxterms.typeThesis
dc.publisher.collegeDarwin
dc.type.qualificationtitlePhD in Biological Science
cam.supervisorLöwe, Jan
rioxxterms.freetoread.startdate2021-12-04


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record