Sandbox 208: Difference between revisions
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== Catalytic mechanism == | == Catalytic mechanism == | ||
In the GDI domain I, the four helices A, C I and N forme a bundle. Helix I and the loop adjacent to the helix C belong to RBP and make direct contact with the GTPase upon its binding. | |||
Rab binding may promote the rearrangement of the GDI helices by pushing helix I toward the GDI core, whereas the loop following helix C is pushed away from the core, resulting in displacement of helices C and N. | |||
The displaced helices C and N make direct contact with domain II of GDI and appear to induce a conformationnal change, resulting in structural reorganization of domain II. | |||
The majority of GDI domain II (helices E, H, G and F) retains its structure upon Rab binding. However, there is a change in its orientation relative to domain I, and helix D is not tighly packed within domain II anymore. | |||
The side chain of Phe192 located in helix G flips and pushes the loop following helix D away, stabilizing the pocket in the open conformation. | |||
Solvent exposure presumably is the reason for the moderate affinity of GDI to unprenylated Rab: the increase affinity of GDI to Rab upon prenyl group binding might be due to the Rab lipid moiety filling the open hydrophobic lipid binding pocket in GDI, diminishing the solvent exposed hydrophobic surfaces of the GDI-Rab complex. The large increase in affinity of GDI to Rab upon prenyl group binding appears to be the driving force for the membrane extraction process. | |||
= Diseases = | = Diseases = | ||