Three-dimensional model of the human platelet integrin alpha IIbbeta 3 based on electron cryomicroscopy and x-ray crystallography.
Integrins are a large family of heterodimeric transmembrane signaling proteins that affect diverse biological processes such as development, angiogenesis, wound healing, neoplastic transformation, and thrombosis. We report here the three-dimensional structure at 20-A resolution of the unliganded, low-affinity state of the human platelet integrin alpha(IIb)beta(3) derived by electron cryomicroscopy and single particle image reconstruction. The large ectodomain and small cytoplasmic domains are connected by a rod of density that we interpret as two parallel transmembrane alpha-helices. The docking of the x-ray structure of the alpha(V)beta(3) ectodomain into the electron cryomicroscopy map of alpha(IIb)beta(3) requires hinge movements at linker regions between domains in the crystal structure. Comparison of the putative high- and low-affinity conformations reveals dramatic conformational changes associated with integrin activation.
Adair
Brian D
BD
The Scripps Research Institute, Department of Cell Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Yeager
Mark
M
D000595:Amino Acid Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D020285:Cryoelectron Microscopy / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D017434:Protein Structure, Tertiary
D019039:Platelet Glycoprotein GPIIb-IIIa Complex