Sandbox Reserved 1493: Difference between revisions
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The '''headpiece''' (2VDL) of integrin αIIbβ3 enables cation-facilitated ligand binding with multiple ligands (most known being [[fibrinogen]], [[fibronectin]], von Willebrand factors, [[thrombospondin]] and vitronectin). Binding affinity is dynamic and depends on the conformational status of the receptor. | The '''headpiece''' (2VDL) of integrin αIIbβ3 enables cation-facilitated ligand binding with multiple ligands (most known being [[fibrinogen]], [[fibronectin]], von Willebrand factors, [[thrombospondin]] and vitronectin). Binding affinity is dynamic and depends on the conformational status of the receptor. | ||
''Jmol displays residues 32-483 of αIIb and residues 27-487 of β3. In order to have a global view of the integrin, | ''Jmol displays residues 32-483 of αIIb and residues 27-487 of β3. In order to have a global view of the integrin, see pictures.'' | ||
<StructureSection load='2vdl' size='340' side='right' caption='2VDL Headpiece of integrin αIIbβ3' scene=''> | <StructureSection load='2vdl' size='340' side='right' caption='2VDL Headpiece of integrin αIIbβ3' scene=''> | ||
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== Function == | == Function == | ||
4 principal '''ligand binding domains''' involved in clotting have been characterized on the extracellular '''headpiece''' of the integrin at the <scene name='80/802667/2vdo_ligand_in_active_site/1'>interface</scene> between the αIIb subunit β propeller and the β3 subunit I domain. | 4 principal '''ligand binding domains''' involved in clotting have been characterized on the extracellular '''headpiece''' of the integrin at the <scene name='80/802667/2vdo_ligand_in_active_site/1'>interface</scene> between the αIIb subunit β propeller and the β3 subunit I domain ''(see picture)''. | ||
Most ligands of integrin αIIbβ3 share the particularity of having at least one '''RGD pattern''' in their protein sequence that can be recognized by the RGD binding site in the β3 subunit. | Most ligands of integrin αIIbβ3 share the particularity of having at least one '''RGD pattern''' in their protein sequence that can be recognized by the RGD binding site in the β3 subunit. | ||
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==== Propagation of activation ==== | ==== Propagation of activation ==== | ||
It opens a hinge in the integrin which triggers a very quick succession of subunit shifts transmitted from the tail to the extracellular headpiece across the transmembrane domain ('''inside-out signaling'''). Movements of helices and loops move the headpiece to an '''extended conformation''' which uncovers the interface between the two subunits containing '''ligand binding sites'''. Integrin is at an '''intermediate affinity state''' (extended conformation, closed headpiece) and can bind ligands. | It opens a hinge in the integrin which triggers a very quick succession of subunit shifts transmitted from the tail to the extracellular headpiece across the transmembrane domain ('''inside-out signaling'''). Movements of helices and loops move the headpiece to an '''extended conformation''' ''(see picture)'' which uncovers the interface between the two subunits containing '''ligand binding sites'''. Integrin is at an '''intermediate affinity state''' (extended conformation, closed headpiece) and can bind ligands. | ||
[[Image:Activation2.png|thumb|right|Activation of the binding site at intermediate affinity]] | [[Image:Activation2.png|thumb|right|Activation of the binding site at intermediate affinity]] | ||
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The initial contact with the ligand is reversible, but then irreversible binding prevents ligand from dissociating. Binding also changes the conformation of the ligand and may unmask new binding regions on it. | The initial contact with the ligand is reversible, but then irreversible binding prevents ligand from dissociating. Binding also changes the conformation of the ligand and may unmask new binding regions on it. | ||
Extracellular proteins such as fibrinogen then enables '''platelets aggregation''' and '''clotting'''. Integrin αIIbβ3 also bridges to other αIIbβ3 of adjacent platelets. | Extracellular proteins such as fibrinogen then enables '''platelets aggregation''' and '''clotting''' ''(see picture)''. Integrin αIIbβ3 also bridges to other αIIbβ3 of adjacent platelets. | ||
[[Image:Plateletsclotting2vdl.png|thumb|right|Clotting]] | [[Image:Plateletsclotting2vdl.png|thumb|right|Clotting]] | ||
