title: The Structure of a Full-length Membrane-embedded Integrin Bound to a Physiological Ligand.
abstract: Increased ligand binding to integrin ("activation") underpins many biological processes, such as leukocyte trafficking, cell migration, host-pathogen interaction, and hemostasis. Integrins exist in several conformations, ranging from compact and bent to extended and open. However, the exact conformation of membrane-embedded, full-length integrin bound to its physiological macromolecular ligand is still unclear. Integrin αIIbβ3, the most abundant integrin in platelets, has been a prototype for integrin activation studies. Using negative stain electron microscopy and nanodisc-embedding to provide a membrane-like environment, we visualized the conformation of full-length αIIbβ3 in both a Mn(2+)-activated, ligand-free state and a Mn(2+)-activated, fibrin-bound state. Activated but ligand-free integrins exist mainly in the compact conformation, whereas fibrin-bound αIIbβ3 predominantly exists in a fully extended, headpiece open conformation. Our results show that membrane-embedded, full-length integrin adopts an extended and open conformation when bound to its physiological macromolecular ligand.
authors.affiliation: Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306-4380 and.
authors.forename: Aguang
authors.initials: A
authors.lastname: Dai
authors.affiliation: Department of Hematology and Oncology, University of California at San Diego, La Jolla, California 92093-0726.
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.affiliation: Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306-4380 and.
authors.forename: Dianne W
authors.initials: DW
authors.lastname: Taylor
authors.affiliation: Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306-4380 and.
authors.forename: Guiqing
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Hematology and Oncology, University of California at San Diego, La Jolla, California 92093-0726.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ginsberg
authors.affiliation: Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306-4380 and. Electronic address: taylor@bio.fsu.edu.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Taylor
mesh_terms: D001792:Blood Platelets / Q000737:chemistry; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008345:Manganese / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D008024:Ligands; D008563:Membrane Lipids; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D008345:Manganese; D005337:Fibrin
keywords: cell adhesion; electron microscopy (EM); fibrin; nanodisc; platelet; signal transduction; αIIbβ3 integrin