Sandbox 208: Difference between revisions
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= Structure = | = Structure = | ||
== Substrate binding == | == Substrate binding == | ||
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GDIs have functional specificity for a particular Rab. Both yeast and mammalians GDIs contains specific residues that contribute to the strength of their interaction with distinct Rab species. | GDIs have functional specificity for a particular Rab. Both yeast and mammalians GDIs contains specific residues that contribute to the strength of their interaction with distinct Rab species. | ||
= Catalytic mechanism = | |||
Initially, Rab is anchored to a target membrane via its lipid moieties. After interactions with its effectors, it returns to the GDP bound form. There is a primary recognition between Rab and GDI: the GTPase domain of Rab is recognized by GDI. GDI binds to Rab via the RBP, forming a low affinity complex. Then, the Rab conserved C terminal AXA box is recognized and bound by the GDI CCR, increasing the complex affinity. Interactions between CCR and the hydrophobic residues of the AXA box lead to a conformation change of the domain II. The GDI lipid binding pocket opens. It is located in the vicinity of the Rab lipid anchor, leading to a favorable situation for lipid transfer. Firstly, the first extracted lipid initially binds to the superficial lipid binding site leading to the formation of a transient high affinity complex still anchored in the membrane. Secondly, this complex is converted into a soluble complex by coordinating transfer of the GDI-bound lipid into the buried binding site. This event facilitates flipping of the second lipid from the membrane to the surface binding site. Thus, a high affinity Rab-GDI complex is formed and released from the membrane. | Initially, Rab is anchored to a target membrane via its lipid moieties. After interactions with its effectors, it returns to the GDP bound form. There is a primary recognition between Rab and GDI: the GTPase domain of Rab is recognized by GDI. GDI binds to Rab via the RBP, forming a low affinity complex. Then, the Rab conserved C terminal AXA box is recognized and bound by the GDI CCR, increasing the complex affinity. Interactions between CCR and the hydrophobic residues of the AXA box lead to a conformation change of the domain II. The GDI lipid binding pocket opens. It is located in the vicinity of the Rab lipid anchor, leading to a favorable situation for lipid transfer. Firstly, the first extracted lipid initially binds to the superficial lipid binding site leading to the formation of a transient high affinity complex still anchored in the membrane. Secondly, this complex is converted into a soluble complex by coordinating transfer of the GDI-bound lipid into the buried binding site. This event facilitates flipping of the second lipid from the membrane to the surface binding site. Thus, a high affinity Rab-GDI complex is formed and released from the membrane. | ||
