Membrane Binding and Cholesterol Sensing Motif in FtsZ: A Novel Mode of Membrane Recruitment for Bacterial FtsZ.

Cell division in bacteria is initiated by constriction of the Z-ring comprising two essential proteins, FtsZ and FtsA. Though the essential function of the Z-ring in bacterial division has been established, the precise roles of FtsZ and FtsA in the constriction process remain elusive. Due to the minimal number of components, FtsZ/FtsA in cell wall-less bacteria is an ideal model system for obtaining mechanistic insights into Z-ring constriction in the absence of a cell wall synthesis machinery. In this study, we undertook a comparative analysis of FtsZ and FtsA protein sequences from 113 mycoplasma species and the corresponding sequences in cell-walled bacteria. We report a phylogenetically distinct group of 12 species that possess a putative membrane binding amphipathic helix at either the N- or C-terminal extensions of the globular FtsZ domain. Importantly, these FtsZs lack conservation of the conserved C-terminal peptide sequence. We experimentally prove that the proposed C-terminal amphipathic helix in () FtsZ exhibits membrane binding. Additionally, we identify a potential cholesterol recognition motif within the C-terminal amphipathic helix region of FtsZ. Our study catalogues the functional variations of membrane attachment by the FtsZ and FtsA system in cell wall-less mycoplasmas and provides a new perspective to dissect the role of FtsZ and FtsA in cell division.

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