title: Three-dimensional model of human platelet integrin alphaIIb beta3 in solution obtained by small angle neutron scattering.
abstract: Integrin alphaIIbbeta3 is the major membrane protein and adhesion receptor at the surface of blood platelets, which after activation plays a key role in platelet plug formation in hemostasis and thrombosis. Small angle neutron scattering (SANS) and shape reconstruction algorithms allowed formation of a low resolution three-dimensional model of whole alphaIIb beta3 in Ca(2+)/detergent solutions. Model projections after 90 degrees rotation along its long axis show an elongated and "arched" form (135 degrees) not observed before and a "handgun" form. This 20-nm-long structure is well defined, despite alphaIIb beta3 multidomain nature and expected segmental flexibility, with the largest region at the top, followed by two narrower and smaller regions at the bottom. Docking of this SANS envelope into the high resolution structure of alphaIIb beta3, reconstructed from crystallographic and NMR data, shows that the solution structure is less constrained, allows tentative assignment of the disposition of the alphaIIb and beta3 subunits and their domains within the model, and points out the structural analogies and differences of the SANS model with the crystallographic models of the recombinant ectodomains of alphaIIb beta3 and alphaV beta3 and with the cryo-electron microscopy model of whole alphaIIb beta3. The ectodomain is in the bent configuration at the top of the model, where alphaIIb and beta3 occupy the concave and convex sides, respectively, at the arched projection, with their bent knees at its apex. It follows the narrower transmembrane region and the cytoplasmic domains at the bottom end. AlphaIIb beta3 aggregated in Mn(2+)/detergent solutions, which impeded to get its SANS model.
authors.affiliation: Departamento de Biofísica, Instituto de Química Física, Consejo Superior de Investigationes Científicas, Serrano 119, Madrid 28006, Spain.
authors.forename: Aurora
authors.initials: A
authors.lastname: Nogales
authors.forename: Carolina
authors.initials: C
authors.lastname: García
authors.forename: Javier
authors.initials: J
authors.lastname: Pérez
authors.forename: Phil
authors.initials: P
authors.lastname: Callow
authors.forename: Tiberio A
authors.initials: TA
authors.lastname: Ezquerra
authors.forename: José
authors.initials: J
authors.lastname: González-Rodríguez
mesh_terms: D006801:Humans; D008958:Models, Molecular; D009502:Neutrons; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry* / Q000235:genetics; D020836:Protein Structure, Quaternary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D012542:Scattering, Radiation
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex