Membrane Tethering of SepF, a Membrane Anchor for the Mycobacterium tuberculosis Z-ring. Issue 21 (15th November 2022)

• Record Type: Journal Article
• Authors: Dey, Souvik; Zhou, Huan-Xiang
• Is Part Of: Journal of molecular biology. Volume 434:Issue 21(2022)
• Publication Date: 2022-11-15
• Subjects: membrane binding -- intrinsically disordered regions -- membrane anchor -- cell division -- Z-ring; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2022.167817
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: Mycobacterial cell division starts with membrane anchoring of Z-ring by SepF. SepF itself is tethered to membrane by both amphipathic helix and disordered linker. Linker tethering keeps Z-ring at close proximity of membrane. Interactions of late-stage membrane proteins with Z-ring can thereby be formed. Abstract: Bacterial cell division begins with the formation of the Z-ring via polymerization of FtsZ and the localization of Z-ring beneath the inner membrane through membrane anchors. In Mycobacterium tuberculosis ( Mtb ), SepF is one such membrane anchor, but our understanding of the underlying mechanism is very limited. Here we used molecular dynamics simulations to characterize how SepF itself, a water-soluble protein, tethers to acidic membranes that mimic the Mtb inner membrane. In addition to an amphipathic helix (residues 1–12) at the N-terminus, membrane binding also occurs through two stretches of positively charged residues (Arg27-Arg37 and Arg95-Arg107) in the long linker preceding the FtsZ-binding core domain (residues 128–218). The additional interactions via the disordered linker stabilize the membrane tethering of SepF, and keep the core domain of SepF and hence the attached Z-ring close to the membrane. The resulting membrane proximity of the Z-ring in turn enables its interactions with and thus recruitment of two membrane proteins, FtsW and CrgA, at the late stage of cell division.