title: An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase.
abstract: LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.
authors.affiliation: Centre for Carbohydrate Recognition and Signalling, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus, Denmark.
authors.forename: Jaslyn E M M
authors.initials: JE
authors.lastname: Wong
authors.affiliation: Niels Bohr Institute, Faculty of Science, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen, Denmark.
authors.forename: Søren Roi
authors.initials: SR
authors.lastname: Midtgaard
authors.affiliation: Centre for Carbohydrate Recognition and Signalling, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus, Denmark.
authors.forename: Kira
authors.initials: K
authors.lastname: Gysel
authors.affiliation: Centre for Carbohydrate Recognition and Signalling, Department of Chemistry, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
authors.forename: Mikkel B
authors.initials: MB
authors.lastname: Thygesen
authors.affiliation: Centre for Carbohydrate Recognition and Signalling, Department of Chemistry, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
authors.forename: Kasper K
authors.initials: KK
authors.lastname: Sørensen
authors.affiliation: Centre for Carbohydrate Recognition and Signalling, Department of Chemistry, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
authors.forename: Knud J
authors.initials: KJ
authors.lastname: Jensen
authors.affiliation: Centre for Carbohydrate Recognition and Signalling, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Stougaard
authors.affiliation: Centre for Carbohydrate Recognition and Signalling, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Thirup
authors.affiliation: Centre for Carbohydrate Recognition and Signalling, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus, Denmark.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Blaise
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D010450:Endopeptidases / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016963:Thermus thermophilus / Q000201:enzymology* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D010450:Endopeptidases
keywords: LysM domains; d,l-endopeptidase