Sandbox 208: Difference between revisions

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We know that GDI deletion can be lethal in yeast (*), whereas a mutation in the alpha-RabGDI gene, residue I100, leads to X-linked nonsyndromic mental retardation in humans. This mutation is characterized by reduced extraction from the membrane. This residue is located in the CCR and is part of a group of nonpolar residues on the surface of the RabGDI molecule that form an extended hydrophic patch with a central cavity on the lower part of domain II. This assembly is involved in binding of the C-terminus of Rab via interaction with Val191 and Leu193 and induces a 90° turn in the C-terminus, which directs it over the effector loop toward the lipid-binding site. Mutation is this hydrophobic patch are expected have a two fold effect.

First, they will ~~impari~~ C-terminus binding and will reduce the affinity of the RabGDI molecule for Rab. Second, and ~~propably~~ more important, they will perturb the orientation of the Rab C-terminus in the vicinity of the effector loop and the lipid-binding domain. This is likely interfere with GTPase interaction with molecules assisting delivery and removal of Rab proteins to and from the membrane.

First, they will impair C-terminus binding and will reduce the affinity of the RabGDI molecule for Rab. Second, and probably more important, they will perturb the orientation of the Rab C-terminus in the vicinity of the effector loop and the lipid-binding domain. This is likely interfere with GTPase interaction with molecules assisting delivery and removal of Rab proteins to and from the membrane.

= Additional 3D Structures of Rab GDP-Dissociation Inhibitor =

Sandbox 208: Difference between revisions

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@@ Line 36: / Line 36: @@
 We know that GDI deletion can be lethal in yeast (*), whereas a mutation in the alpha-RabGDI gene, residue I100, leads to X-linked nonsyndromic mental retardation in humans. This mutation is characterized by reduced extraction from the membrane. This residue is located in the CCR and is part of a group of nonpolar residues on the surface of the RabGDI molecule that form an extended hydrophic patch with a central cavity on the lower part of domain II. This assembly is involved in binding of the C-terminus of Rab via interaction with Val191 and Leu193 and  induces a 90° turn in the C-terminus, which directs it over the effector loop toward the lipid-binding site. Mutation is this hydrophobic patch are expected have a two fold effect.
-First, they will impari C-terminus binding and will reduce the affinity of the RabGDI molecule for Rab. Second, and propably more important, they will perturb the orientation of the Rab C-terminus in the vicinity of the effector loop and the lipid-binding domain. This is likely interfere with GTPase interaction with molecules assisting delivery and removal of Rab proteins to and from the membrane.
+First, they will impair C-terminus binding and will reduce the affinity of the RabGDI molecule for Rab. Second, and probably more important, they will perturb the orientation of the Rab C-terminus in the vicinity of the effector loop and the lipid-binding domain. This is likely interfere with GTPase interaction with molecules assisting delivery and removal of Rab proteins to and from the membrane.
 = Additional 3D Structures of Rab GDP-Dissociation Inhibitor =