Natural Sciences and Engineering Research Council (NSERC, Canada)
Canada
Canadian Institutes of Health Research (CIHR)
Canada
Howard Hughes Medical Institute (HHMI)
United States
Canada Research Chairs
Canada
Citation
Journal: Sci Adv / Year: 2024 Title: Cryo-EM analysis of TarL, a polymerase in wall teichoic acid biogenesis central to virulence and antibiotic resistance. Authors: Franco K K Li / Liam J Worrall / Robert T Gale / Eric D Brown / Natalie C J Strynadka / Abstract: Wall teichoic acid (WTA), a covalent adduct of Gram-positive bacterial cell wall peptidoglycan, contributes directly to virulence and antibiotic resistance in pathogenic species. Polymerization of ...Wall teichoic acid (WTA), a covalent adduct of Gram-positive bacterial cell wall peptidoglycan, contributes directly to virulence and antibiotic resistance in pathogenic species. Polymerization of the WTA ribitol-phosphate chain is catalyzed by TarL, a member of the largely uncharacterized TagF-like family of membrane-associated enzymes. We report the cryo-electron microscopy structure of TarL, showing a tetramer that forms an extensive membrane-binding platform of monotopic helices. TarL is composed of an amino-terminal immunoglobulin-like domain and a carboxyl-terminal glycosyltransferase-B domain for ribitol-phosphate polymerization. The active site of the latter is complexed to donor substrate cytidine diphosphate-ribitol, providing mechanistic insights into the catalyzed phosphotransfer reaction. Furthermore, the active site is surrounded by electropositive residues that serve to retain the lipid-linked acceptor for polymerization. Our data advance general insight into the architecture and membrane association of the still poorly characterized monotopic membrane protein class and present molecular details of ribitol-phosphate polymerization that may aid in the design of new antimicrobials.
B: CDP-glycerol glycerophosphotransferase family protein A: CDP-glycerol glycerophosphotransferase family protein C: CDP-glycerol glycerophosphotransferase family protein D: CDP-glycerol glycerophosphotransferase family protein E: CDP-glycerol glycerophosphotransferase family protein F: CDP-glycerol glycerophosphotransferase family protein G: CDP-glycerol glycerophosphotransferase family protein H: CDP-glycerol glycerophosphotransferase family protein I: CDP-glycerol glycerophosphotransferase family protein J: CDP-glycerol glycerophosphotransferase family protein