ZipA Uses a Two-Pronged FtsZ-Binding Mechanism Necessary for Cell Division

Abstract

The tubulin homolog FtsZ plays a central early role in organizing bacterial cell division proteins at the cytoplasmic membrane. However, FtsZ does not directly interact with the membrane itself, instead relying on proteins such as FtsA to tether it to the membrane.

An Arg/Ala-Rich Helix in the N-Terminal Region ofM. tuberculosisFtsQ Anchors FtsZ to Membranes

“…We then turned to solid-state NMR spectroscopy using both magic-angle spinning (MAS) and oriented samples. When uniformly 13 C-labeled FtsQ1-99 is bound to 7:3 POPG/POPC vesicles, residues that remain dynamic appear in an INEPT 13 C-13 C correlation spectrum acquired on MAS samples (Figs. 5A and S5, blue crosspeaks).…”

“…For example, the Alab-a, Argb-a, and Glub-a cross peaks are at (51.83, 18.76), (55.34, 30.40), and (55.93, 29.86), respectively, and are close to the average (Ca, Cb) chemical shifts, (52.3 ± 0.1, 19.0 ± 0.1), (56.2 ± 0.4, 30.6 ± 0.1), and (56.1 ± 0.9, 30.0 ± 0.3), of Ala, Arg, and Glu in nonhelical regions (Table S2). In a cross-polarization (CP) 13 C-13 C correlation spectrum, which reports on residues that are rigid in membrane-bound FtsQ1-99, there are far fewer crosspeaks (Fig. 5A, red crosspeaks; Fig.…”

“…FtsZ uses its disordered C-tail to bind a structured domain in each of these three proteins for membrane anchoring (11)(12)(13). In E. coli, FtsA and ZipA provide redundancy in membrane anchoring, as Z-rings can form in the absence of either one of them but not both (6).…”

“…More specifically, it binds to the GTPase domain (residues 1-312), not to the disordered C-tail (residues 313-379) of FtsZ. The participation of the FtsZ GTPase domain in binding with another divisome protein is unusual, as it is the C-tail that binds with FtsA, ZipA, and SepF for the membrane anchoring of FtsZ (11)(12)(13)15) and with FtsW at the late stage of cell division (16).…”

Membrane Tethering of SepF, a Membrane Anchor for the Mycobacterium tuberculosis Z-ring

“…ZipA is a transmembrane protein [4], whereas FtsA and SepF are water-soluble proteins with an amphipathic helix for membrane tethering [5, 6]. FtsZ uses its disordered C-tail to bind a structured domain in each of these three proteins for membrane anchoring [6-8]. The role of SepF as a membrane anchor of the Z-ring has also been characterized for the homolog in Corynebacterium glutamicum ( Cgl ) [9].…”