title: Crystal Structure of the Heterotrimeric Integrin-Binding Region of Laminin-111.
abstract: Laminins are cell-adhesive glycoproteins that are essential for basement membrane assembly and function. Integrins are important laminin receptors, but their binding site on the heterotrimeric laminins is poorly defined structurally. We report the crystal structure at 2.13 Å resolution of a minimal integrin-binding fragment of mouse laminin-111, consisting of ∼50 residues of α1β1γ1 coiled coil and the first three laminin G-like (LG) domains of the α1 chain. The LG domains adopt a triangular arrangement, with the C terminus of the coiled coil situated between LG1 and LG2. The critical integrin-binding glutamic acid residue in the γ1 chain tail is surface exposed and predicted to bind to the metal ion-dependent adhesion site in the integrin β1 subunit. Additional contacts to the integrin are likely to be made by the LG1 and LG2 surfaces adjacent to the γ1 chain tail, which are notably conserved and free of obstructing glycans.
authors.affiliation: Department of Life Sciences, Imperial College London, Sir Ernst Chain Building, London SW7 2AZ, UK.
authors.forename: David
authors.initials: D
authors.lastname: Pulido
authors.affiliation: Department of Life Sciences, Imperial College London, Sir Ernst Chain Building, London SW7 2AZ, UK.
authors.forename: Sadaf-Ahmahni
authors.initials: SA
authors.lastname: Hussain
authors.affiliation: Department of Life Sciences, Imperial College London, Sir Ernst Chain Building, London SW7 2AZ, UK. Electronic address: e.hohenester@imperial.ac.uk.
authors.forename: Erhard
authors.initials: E
authors.lastname: Hohenester
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D002460:Cell Line; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary
chemical_list: D016023:Integrins; D007797:Laminin
keywords: cell adhesion; coiled coil; extracellular matrix; integrin; laminin