title: Protein sorting to the cell wall envelope of Gram-positive bacteria.
abstract: The covalent anchoring of surface proteins to the cell wall envelope of Gram-positive bacteria occurs by a universal mechanism requiring sortases, extracellular transpeptidases that are positioned in the plasma membrane. Surface protein precursors are first initiated into the secretory pathway of Gram-positive bacteria via N-terminal signal peptides. C-terminal sorting signals of surface proteins, bearing an LPXTG motif or other recognition sequences, provide for sortase-mediated cleavage and acyl enzyme formation, a thioester linkage between the active site cysteine residue of sortase and the C-terminal carboxyl group of cleaved surface proteins. During cell wall anchoring, sortase acyl enzymes are resolved by the nucleophilic attack of peptidoglycan substrates, resulting in amide bond formation between the C-terminal end of surface proteins and peptidoglycan cross-bridges within the bacterial cell wall envelope. The genomes of Gram-positive bacteria encode multiple sortase genes. Recent evidence suggests that sortase enzymes catalyze protein anchoring reactions of multiple different substrate classes with different sorting signal motif sequences, protein linkage to unique cell wall anchor structures as well as protein polymerization leading to the formation of pili on the surface of Gram-positive bacteria.
authors.affiliation: Committee on Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
authors.forename: Hung
authors.initials: H
authors.lastname: Ton-That
authors.forename: Luciano A
authors.initials: LA
authors.lastname: Marraffini
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
mesh_terms: D019881:Aminoacyltransferases / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D003546:Cysteine Endopeptidases; D010861:Fimbriae, Bacterial / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000502:physiology*; D025301:Hyphae / Q000378:metabolism; D021382:Protein Sorting Signals; D021381:Protein Transport / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D021382:Protein Sorting Signals; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases