title: Aromatic amino acids at the surface of InlB are essential for host cell invasion by Listeria monocytogenes.
abstract: The surface protein InlB of the pathogen Listeria monocytogenes promotes invasion of this bacterium into host cells by binding to and activating the receptor tyrosine kinase Met. The curved leucine-rich repeat (LRR) domain of InlB, which is essential for this process, contains a string of five surface-exposed aromatic amino acid residues positioned along its concave face. Here, we show that the replacement of four of these residues (F104, W124, Y170 or Y214) by serine leads to a complete loss of uptake of latex beads coated with InlB', a truncated functional variant of InlB. The mutants correspondingly display severely reduced binding to Met. To abrogate fully invasion of bacteria expressing full-length InlB, exchange of at least four aromatic amino acids is required. We conclude that InlB binds to Met through its concave surface of the LRR domain, and that aromatic amino acids are critical for binding and signalling before invasion.
authors.affiliation: Department of Structural Biology, German Research Centre for Biotechnology (GBF), Mascheroder Weg 1, D-38124 Braunschweig, Germany.
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Machner
authors.forename: Susanne
authors.initials: S
authors.lastname: Frese
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Schubert
authors.forename: Veronique
authors.initials: V
authors.lastname: Orian-Rousseau
authors.forename: Ermanno
authors.initials: E
authors.lastname: Gherardi
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wehland
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Niemann
authors.forename: Dirk W
authors.initials: DW
authors.lastname: Heinz
mesh_terms: D019943:Amino Acid Substitution; D024322:Amino Acids, Aromatic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins; D018360:Crystallography, X-Ray; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D008089:Listeria monocytogenes / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D015398:Signal Transduction; D020349:Surface Plasmon Resonance
chemical_list: D024322:Amino Acids, Aromatic; D001426:Bacterial Proteins; D008565:Membrane Proteins; C095768:inlB protein, Listeria monocytogenes; D019859:Proto-Oncogene Proteins c-met