title: The structure of integrin α1I domain in complex with a collagen-mimetic peptide.
abstract: We have determined the structure of the human integrin α1I domain bound to a triple-helical collagen peptide. The structure of the α1I-peptide complex was investigated using data from NMR, small angle x-ray scattering, and size exclusion chromatography that were used to generate and validate a model of the complex using the data-driven docking program, HADDOCK (High Ambiguity Driven Biomolecular Docking). The structure revealed that the α1I domain undergoes a major conformational change upon binding of the collagen peptide. This involves a large movement in the C-terminal helix of the αI domain that has been suggested to be the mechanism by which signals are propagated in the intact integrin receptor. The structure suggests a basis for the different binding selectivity observed for the α1I and α2I domains. Mutational data identify residues that contribute to the conformational change observed. Furthermore, small angle x-ray scattering data suggest that at low collagen peptide concentrations the complex exists in equilibrium between a 1:1 and 2:1 α1I-peptide complex.
authors.affiliation: From Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences and.
authors.forename: Yanni K-Y
authors.initials: YK
authors.lastname: Chin
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Headey
authors.forename: Biswaranjan
authors.initials: B
authors.lastname: Mohanty
authors.forename: Rahul
authors.initials: R
authors.lastname: Patil
authors.forename: Paul A
authors.initials: PA
authors.lastname: McEwan
authors.forename: James D
authors.initials: JD
authors.lastname: Swarbrick
authors.forename: Terrence D
authors.initials: TD
authors.lastname: Mulhern
authors.forename: Jonas
authors.initials: J
authors.lastname: Emsley
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Simpson
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Scanlon
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism; D003094:Collagen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D039423:Integrin alpha1 / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D039423:Integrin alpha1; D010455:Peptides; D003094:Collagen
keywords: Collagen; Extracellular Matrix; Integrins; NMR; Protein Structure; Protein-Protein Interactions