title: OmpA: A Flexible Clamp for Bacterial Cell Wall Attachment.
abstract: The envelope of Gram-negative bacteria is highly complex, containing separate outer and inner membranes and an intervening periplasmic space encompassing a peptidoglycan (PGN) cell wall. The PGN scaffold is anchored non-covalently to the outer membrane via globular OmpA-like domains of various proteins. We report atomically detailed simulations of PGN bound to OmpA in three different states, including the isolated C-terminal domain (CTD), the full-length monomer, or the complete full-length dimeric form. Comparative analysis of dynamics of OmpA CTD from different bacteria helped to identify a conserved PGN-binding mode. The dynamics of full-length OmpA, embedded within a realistic representation of the outer membrane containing full-rough (Ra) lipopolysaccharide, phospholipids, and cardiolipin, suggested how the protein may provide flexible mechanical support to the cell wall. An accurate model of the heterogeneous bacterial cell envelope should facilitate future efforts to develop antibacterial agents.
authors.affiliation: School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK.
authors.forename: Firdaus
authors.initials: F
authors.lastname: Samsudin
authors.affiliation: School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK.
authors.forename: Maite L
authors.initials: ML
authors.lastname: Ortiz-Suarez
authors.affiliation: School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK; CBR Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Piggot
authors.affiliation: Bioinformatics Institute (A(∗)STAR), 30 Biopolis Street, 07-01 Matrix, Singapore 138671, Singapore; National University of Singapore, Department of Biological Sciences, 14 Science Drive 4, Singapore 117543, Singapore. Electronic address: peterjb@bii.a-star.edu.sg.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bond
authors.affiliation: School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK. Electronic address: s.khalid@soton.ac.uk.
authors.forename: Syma
authors.initials: S
authors.lastname: Khalid
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D019281:Dimerization; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010457:Peptidoglycan / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains
chemical_list: D001425:Bacterial Outer Membrane Proteins; D010457:Peptidoglycan; C078167:OMPA outer membrane proteins
keywords: Escherichia coli; OmpA; bacterial cell envelope; cell wall; molecular dynamics; outer membrane; peptidoglycan; simulation