Structural basis of peptidoglycan synthesis by E. coli RodA-PBP2 complex.

Autor: Nygaard R; Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY, 10032, USA., Graham CLB; School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK., Belcher Dufrisne M; Department of Chemistry and Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, 22904, USA., Colburn JD; School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK.; Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK., Pepe J; Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY, 10032, USA., Hydorn MA; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, 10032, USA., Corradi S; Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY, 10032, USA.; Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy., Brown CM; School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK.; Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK., Ashraf KU; Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY, 10032, USA., Vickery ON; School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK.; Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK., Briggs NS; School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK., Deering JJ; School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK., Kloss B; New York Consortium on Membrane Protein Structure, New York Structural Biology Center, 89 Convent Avenue, New York, NY, 10027, USA., Botta B; Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy., Clarke OB; Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY, 10032, USA.; Department of Anesthesiology, Columbia University Irving Medical Center, New York, NY, 10032, USA., Columbus L; Department of Chemistry and Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, 22904, USA. columbus@virginia.edu., Dworkin J; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, 10032, USA. jonathan.dworkin@columbia.edu., Stansfeld PJ; School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK. phillip.stansfeld@warwick.ac.uk.; Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK. phillip.stansfeld@warwick.ac.uk., Roper DI; School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK. David.roper@warwick.ac.uk., Mancia F; Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY, 10032, USA. fm123@columbia.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Aug 24; Vol. 14 (1), pp. 5151. Date of Electronic Publication: 2023 Aug 24.
DOI: 10.1038/s41467-023-40483-8
Abstrakt: Peptidoglycan (PG) is an essential structural component of the bacterial cell wall that is synthetized during cell division and elongation. PG forms an extracellular polymer crucial for cellular viability, the synthesis of which is the target of many antibiotics. PG assembly requires a glycosyltransferase (GT) to generate a glycan polymer using a Lipid II substrate, which is then crosslinked to the existing PG via a transpeptidase (TP) reaction. A Shape, Elongation, Division and Sporulation (SEDS) GT enzyme and a Class B Penicillin Binding Protein (PBP) form the core of the multi-protein complex required for PG assembly. Here we used single particle cryo-electron microscopy to determine the structure of a cell elongation-specific E. coli RodA-PBP2 complex. We combine this information with biochemical, genetic, spectroscopic, and computational analyses to identify the Lipid II binding sites and propose a mechanism for Lipid II polymerization. Our data suggest a hypothesis for the movement of the glycan strand from the Lipid II polymerization site of RodA towards the TP site of PBP2, functionally linking these two central enzymatic activities required for cell wall peptidoglycan biosynthesis.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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