Epitopes described in "Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics."

Article Authors:Tsan Xiao; Junichi Takagi; Barry S Coller; Jia-Huai Wang; Timothy A Springer
Article Title:Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics.
Reference Detail
Reference ID:356
Abstract:Integrins are important adhesion receptors in all Metazoa that transmit conformational change bidirectionally across the membrane. Integrin alpha and beta subunits form a head and two long legs in the ectodomain and span the membrane. Here, we define with crystal structures the atomic basis for allosteric regulation of the conformation and affinity for ligand of the integrin ectodomain, and how fibrinogen-mimetic therapeutics bind to platelet integrin alpha(IIb)beta3. Allostery in the beta3 I domain alters three metal binding sites, associated loops and alpha1- and alpha7-helices. Piston-like displacement of the alpha7-helix causes a 62 degrees reorientation between the beta3 I and hybrid domains. Transmission through the rigidly connected plexin/semaphorin/integrin (PSI) domain in the upper beta3 leg causes a 70 A separation between the knees of the alpha and beta legs. Allostery in the head thus disrupts interaction between the legs in a previously described low-affinity bent integrin conformation, and leg extension positions the high-affinity head far above the cell surface.
Reference Type:Literature
PubMed ID:15378069
Journal Volume:432
Article Pages:59-67
Journal ISSN:1476-4687
Article Chemical List:Ligands;Platelet Glycoprotein GPIIb-IIIa Complex;Fibrinogen;Magnesium;Calcium
Article MeSH List:Allosteric Regulation; Allosteric Site; Amino Acid Sequence; Biomimetic Materials(chemistry; metabolism); Calcium(metabolism); Crystallography, X-Ray; Fibrinogen(chemistry); Ligands; Magnesium(metabolism); Models, Molecular; Molecular Sequence Data; Platelet Glycoprotein GPIIb-IIIa Complex(chemistry; metabolism); Protein Structure, Quaternary; Protein Structure, Tertiary
Article Comments:15525967 Nature. 2004 Nov 4;432(7013):27-8
Curation Last Updated:2014-10-03 19:32:45