Sandbox 208
From Proteopedia
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= Biological role = | = Biological role = | ||
| - | Rab-GDI does not facilitate Rab prenylation, but serves as a generic regulator for recycling of | + | Rab-GDI does not facilitate Rab prenylation, but serves as a generic regulator for recycling of Rab-GTPases for use in multiple rounds of membrane transport. It retrieves Rabs in the GDP-bound form from the membrane and delivers it to the cytosol, controlling the distribution of Rabs between membranes and cytosol. GDI is believed to be stably only with GDP-loaded and prenylated Rabs proteins, ensuring retrieval of inactivated Rab GTPases from the membrane at the end of their functionnal cycle. Rab-GDI is critically important for the proper functionning of the vesicular transport machinery, and its deletion can be lethal. |
= Structure = | = Structure = | ||
== General structure == | == General structure == | ||
| - | == Substrate binding | + | == Substrate binding == |
| - | == | + | GDI binds the Rab molecule via three interaction sites: |
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| + | '''GDI-Rab Binding Platform (RBP)''', located in domain I, which interacts extensively with the globular part of the Rab molecule. | ||
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| + | '''GDI C-terminus Coordinating Region (CCR)''', located in the cleft between domain I and domain II, which coordinates the flexible extended C-terminus of Rab. It is formed by residues 93-112 from domain I and 226-235 from domain II and reprent a hydrophobic cavity on the surface of the protein located between the GDI domains. Hydrophobic contacts between GDI and Rab are supported by a hydrogen bond involving main chain atoms. | ||
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| + | '''Domain II of GDI''', consisting solely of alpha helices, which form a prenyl-lipid binding pocket, exhibiting an open conformation and accomodating the prenyl moiety of a modified Rab if present. | ||
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| + | == Catalytic mechanism == | ||
= Diseases = | = Diseases = | ||
Revision as of 16:02, 1 December 2011
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Rab-Guanosine biphosphate Dissociation Inhibitor (or Rab-GDI) is an inhibitory protein which facilitated extraction of prenylated GDP-bounds inactive conformation of Rab small GTPase from membranes. This molecule has an important role in vesicular membrane trafficking. It delivers Rab to new formes vesicles (for exocytic and endocytic pathways), where it becomes activated to the GTP-bound form to promote the recuitment of effectors that facilitate vesicle transport through the cytoplasm by the cytoskeleton. This inhibition can be removed by the action of a GEF.
Contents |
Biological role
Rab-GDI does not facilitate Rab prenylation, but serves as a generic regulator for recycling of Rab-GTPases for use in multiple rounds of membrane transport. It retrieves Rabs in the GDP-bound form from the membrane and delivers it to the cytosol, controlling the distribution of Rabs between membranes and cytosol. GDI is believed to be stably only with GDP-loaded and prenylated Rabs proteins, ensuring retrieval of inactivated Rab GTPases from the membrane at the end of their functionnal cycle. Rab-GDI is critically important for the proper functionning of the vesicular transport machinery, and its deletion can be lethal.
Structure
General structure
Substrate binding
GDI binds the Rab molecule via three interaction sites:
GDI-Rab Binding Platform (RBP), located in domain I, which interacts extensively with the globular part of the Rab molecule.
GDI C-terminus Coordinating Region (CCR), located in the cleft between domain I and domain II, which coordinates the flexible extended C-terminus of Rab. It is formed by residues 93-112 from domain I and 226-235 from domain II and reprent a hydrophobic cavity on the surface of the protein located between the GDI domains. Hydrophobic contacts between GDI and Rab are supported by a hydrogen bond involving main chain atoms.
Domain II of GDI, consisting solely of alpha helices, which form a prenyl-lipid binding pocket, exhibiting an open conformation and accomodating the prenyl moiety of a modified Rab if present.
