Sandbox Reserved 1493: Difference between revisions

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== Integrin αIIbβ3 Headpiece (2VDL) ==

Integrin αIIbβ3 (or glycoprotein IIb/IIIa) is a complex present on the membrane of platelets that intervenes in the activation, adherence and aggregation of platelets during clotting. It is a cation-dependant heterodimeric transmembrane receptor containing a large extracellular headpiece and short intracellular tails. It is synthesized in megakaryocytes.

'''Integrin αIIbβ3''' (or glycoprotein IIb/IIIa) is a complex present on the membrane of platelets that intervenes in the activation, adherence and aggregation of platelets during clotting. It is a cation-dependant heterodimeric transmembrane receptor containing a large extracellular headpiece and short intracellular tails. It is synthesized in megakaryocytes.

Its particular shape and localisation on the membrane allows both ~~ligand binding and~~ transduction of the activation signal. It is the dominant integrin on platelets with 70,000 to 90,000 receptors expressed on each platelet in the resting state.

Its particular shape and localisation on the membrane allows both transduction of the intracellular activation signal and extracellular ligand binding. It is the dominant integrin on platelets with 70,000 to 90,000 receptors expressed on each platelet in the resting state.

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.

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== Disease and relevance ==

=== Glanzmann thrombasthenia ===

Glanzmann thrombasthenia is a hemorrhagic disease characterized by a lack of αIIbβ3 complexes on the membrane of platelets, an absence of fibrinogen and an inability to retract a clot. This deficiency is caused by mutation in the sequence of the integrin. Multiple amino acids can be affected. Here are two examples of consequences:

* Pro-145 mutation at an Ala of the W3:4-1 loop and Leu-183 mutation at a Pro of a surrounding loop cause insertion of two amino acid residues into the first loop (residues 147 to 166) and modifies loop conformations. It results in a reduction in the expression level of integrin αIIbβ3.

* mutation of the Arg 724 terminus of the β3 subunit which generates a truncated integrin composed only of the first 8 of the 47 amino acids normally present in its cytoplasmic domain.

=== Inhibitors ===

αIIbβ3 is a target of blocker drugs such as Abciximab (chimeric Fab fragment), Eptifibatide (synthetic peptide inhibitor) and Tirofiban (synthetic non-peptide inhibitor). Such antagonists inhibit the binding of fibrinogen to αIIbβ3 and thus platelet aggregation.

These drugs are currently prescribed to patients with acute coronary syndromes (ACS), Cardiovascular diseases (CVD) such as myocardial infarction, or to patients who undergo PCI or other thrombotic diseases.

</StructureSection>

Sandbox Reserved 1493: Difference between revisions

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@@ Line 2: / Line 2: @@
 == Integrin αIIbβ3 Headpiece (2VDL) ==
-Integrin αIIbβ3 (or glycoprotein IIb/IIIa) is a complex present on the membrane of platelets that intervenes in the activation, adherence and aggregation of platelets during clotting. It is a cation-dependant heterodimeric transmembrane receptor containing a large extracellular headpiece and short intracellular tails. It is synthesized in megakaryocytes.
+'''Integrin αIIbβ3''' (or glycoprotein IIb/IIIa) is a complex present on the membrane of platelets that intervenes in the activation, adherence and aggregation of platelets during clotting. It is a cation-dependant heterodimeric transmembrane receptor containing a large extracellular headpiece and short intracellular tails. It is synthesized in megakaryocytes.
-Its particular shape and localisation on the membrane allows both ligand binding and transduction of the activation signal. It is the dominant integrin on platelets with 70,000 to 90,000 receptors expressed on each platelet in the resting state.
+Its particular shape and localisation on the membrane allows both transduction of the intracellular activation signal and extracellular ligand binding. It is the dominant integrin on platelets with 70,000 to 90,000 receptors expressed on each platelet in the resting state.
-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.
 <StructureSection load='2vdl' size='340' side='right' caption='2VDL Headpiece of integrin αIIbβ3' scene=''>
@@ Line 118: / Line 118: @@
 == Disease and relevance ==
+=== Glanzmann thrombasthenia ===
+Glanzmann thrombasthenia is a hemorrhagic disease characterized by a lack of αIIbβ3 complexes on the membrane of platelets, an absence of fibrinogen and an inability to retract a clot. This deficiency is caused by mutation in the sequence of the integrin. Multiple amino acids can be affected. Here are two examples of consequences:
+* Pro-145 mutation at an Ala of the W3:4-1 loop and Leu-183 mutation at a Pro of a surrounding loop cause insertion of two amino acid residues into the first loop (residues 147 to 166) and modifies loop conformations. It results in a reduction in the expression level of integrin αIIbβ3.
+* mutation of the Arg 724 terminus of the β3 subunit which generates a truncated integrin composed only of the first 8 of the 47 amino acids normally present in its cytoplasmic domain.
+=== Inhibitors ===
+αIIbβ3 is a target of blocker drugs such as Abciximab (chimeric Fab fragment), Eptifibatide (synthetic peptide inhibitor) and Tirofiban (synthetic non-peptide inhibitor). Such antagonists inhibit the binding of fibrinogen to αIIbβ3 and thus platelet aggregation.
+These drugs are currently prescribed to patients with acute coronary syndromes (ACS), Cardiovascular diseases (CVD) such as myocardial infarction, or to patients who undergo PCI or other thrombotic diseases.
 </StructureSection>