1tye
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| , resolution 2.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | ITGAB (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structural basis for allostery in integrins and binding of ligand-mimetic therapeutics to the platelet receptor for fibrinogen
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Glanzmann thrombasthenia, type A OMIM:[607759], Glanzmann thrombasthenia, type B OMIM:[173470], Thrombocytopenia, neonatal alloimmune OMIM:[607759]
About this StructureAbout this Structure
1TYE is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics., Xiao T, Takagi J, Coller BS, Wang JH, Springer TA, Nature. 2004 Nov 4;432(7013):59-67. Epub 2004 Sep 19. PMID:15378069
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