8gcd: Difference between revisions
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN] Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface. | [https://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN] Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface. | ||
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== Publication Abstract from PubMed == | |||
Integrin alphaIIbbeta3 is the key receptor regulating platelet retraction and accumulation and a proven drug-target for antithrombotic therapies. Here we resolve the cryo-EM structures of the full-length alphaIIbbeta3, which covers three distinct states along the activation pathway. Firstly, we obtain the alphaIIbbeta3 structure at 3 A resolution in the inactive state, revealing the overall topology of the heterodimer with the transmembrane (TM) helices and the ligand-binding domain tucked in a specific angle proximity to the TM region. After the addition of a Mn(2+) agonist, we resolve two coexisting structures representing two new states between inactive and active state. Our structures show conformational changes of the alphaIIbbeta3 activating trajectory and a unique twisting of the integrin legs, which is required for platelets accumulation. Our structure provides direct structural evidence for how the lower legs are involved in full-length integrin activation mechanisms and offers a new strategy to target the alphaIIbbeta3 lower leg. | |||
Full-length alphaIIbbeta3 cryo-EM structure reveals intact integrin initiate-activation intrinsic architecture.,Huo T, Wu H, Moussa Z, Sen M, Dalton V, Wang Z Structure. 2024 Jul 11;32(7):899-906.e3. doi: 10.1016/j.str.2024.03.006. Epub , 2024 Apr 4. PMID:38579706<ref>PMID:38579706</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | == References == | ||
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