Sandbox Reserved 1493: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 45: | Line 45: | ||
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. | ||
[[Image: | [[Image:Binding_sites1.png|thumb|right|Domains and ligand binding sites of integrin αIIbβ3]] | ||
=== Cation binding sites === | === Cation binding sites === | ||
| Line 88: | Line 88: | ||
It opens a hinge in the integrin which triggers a very quick succession of subunit shifts that are transmitted from the tail to the extracellular headpiece across the transmembrane domain (inside-out signaling). Movements of helices and loops moves the headpiece to an extended conformation which uncovers the interface between the two subunits countaining 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 that are transmitted from the tail to the extracellular headpiece across the transmembrane domain (inside-out signaling). Movements of helices and loops moves the headpiece to an extended conformation which uncovers the interface between the two subunits countaining ligand binding sites. Integrin is at an intermediate affinity state (extended conformation, closed headpiece) and can bind ligands. | ||
[[Image: | [[Image:Activation1.png|thumb|right|Activation of the binding site at intermediate affinity]] | ||
The precise mechanisms of activation which occur in the extracellular part of the integrin remain a mystery. Still, the conformational difference of a disulfide-bonded knot localised in the cysteine-rich core of the β3 subunit between inactivation and activation suggests that this region plays a part in activation. It is thought that the cysteine core of the β3 subunit linked to its N-terminal extremity apply a conformational constraint on the ligand binding site. It includes a few cysteines that remain unpaired and which redox state influence the activation of the integrin, which supposed this region could host a redox site. | The precise mechanisms of activation which occur in the extracellular part of the integrin remain a mystery. Still, the conformational difference of a disulfide-bonded knot localised in the cysteine-rich core of the β3 subunit between inactivation and activation suggests that this region plays a part in activation. It is thought that the cysteine core of the β3 subunit linked to its N-terminal extremity apply a conformational constraint on the ligand binding site. It includes a few cysteines that remain unpaired and which redox state influence the activation of the integrin, which supposed this region could host a redox site. | ||
| Line 100: | Line 100: | ||
Extracellular proteins such as fibrinogen enables platelets aggregation and clotting. Integrin αIIbβ3 also bridges to other αIIbβ3 of adjacent platelets. | Extracellular proteins such as fibrinogen enables platelets aggregation and clotting. Integrin αIIbβ3 also bridges to other αIIbβ3 of adjacent platelets. | ||
[[Image: | [[Image:Plateletsclotting2vdl.png|thumb|right|Clotting]] | ||
Activation mostly occurs via modulation of affinity, but is also affected by avidity for ligand due to receptor clustering by multivalent ligands and changes in membrane fluidity. | Activation mostly occurs via modulation of affinity, but is also affected by avidity for ligand due to receptor clustering by multivalent ligands and changes in membrane fluidity. | ||
