Sandbox 208: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Charlotte Simonin, Lucie Maubert

@@ Line 42: / Line 42: @@
 *'''GDI-Rab Binding Platform (RBP)''', with β strands e1 and e3 and helix C, which form a separate binding site. This platform is located in domain I and interacts with the globular part of the Rab molecule. The RabGDI binding epitope contains a great number of conserved residues on Rab: Ile41, Gly42, Asp/Glu44 and Phe45 from Switch I; Trp62, Asp63, Ala65, Gln67, Phe/Tyr70, Thr/Ala72, Thr74, Ser/Thr75, Ser/Ala76 and Arg79 from Switch II. More precisely, the RBP is an essential structural element which form a great number of interactions with the C-terminus and Switch I of Rab. Three additional invariable residues are located on RBP, and form hydrogen bonds with the switch I region and the C-terminus of Rab.
-*'''GDI C-terminus Coordinating Region (CCR) or C-terminus Binding Region (CBR)'''. The CBR represents a hydrophobic cavity on the GDI surface. In fact, this region is located in the cleft between domain I and domain II. It is formed by <scene name='Sandbox_208/Residues_93-112_domain_i/1'>residues 93-112</scene> from domain I and <scene name='Sandbox_208/Residues_226-235_domain_ii/1'>residues 226-235</scene> from domain II. The CBR coordinates the flexible extended C-terminus of Rab. In most cases, the CBR is occupied by side chains of hydrophobic residues of the Rab C-terminus tail. Hydrophobic contacts between GDI and Rab are supported by a hydrogen bond involving main chain atoms. Rab primary structure analysis revealed the presence of a Rab C-terminus characteristic sequence (AXA box), with two conserved aliphatic amino acid residues (<scene name='Sandbox_208/Val191/1'>Val191</scene> and <scene name='Sandbox_208/Leu193/1'>Leu193</scene>). Mutations of one of these residues induce a decrease of Rab affinity to GDI. Therefore, the AXA box contributes to increase Rab binding affinity to GDI upon complex formation.
+*'''GDI C-terminus Coordinating Region (CCR) or C-terminus Binding Region (CBR)'''. The CBR represents a hydrophobic cavity on the GDI surface. In fact, this region is located in the cleft between domain I and domain II. It is formed by <scene name='Sandbox_208/Residues_93-112_domain_i/1'>residues 93-112</scene> from domain I and <scene name='Sandbox_208/Residues_226-235_domain_ii/1'>residues 226-235</scene> from domain II. The CBR coordinates the flexible extended C-terminus of Rab. In most cases, the CBR is occupied by side chains of hydrophobic residues of the Rab C-terminus tail. Hydrophobic contacts between GDI and Rab are supported by a hydrogen bond involving main chain atoms. Rab primary structure analysis revealed the presence of a Rab C-terminus characteristic sequence (AXA box), with two conserved aliphatic amino acid residues (Val191 and Leu193). Mutations of one of these residues induce a decrease of Rab affinity to GDI. Therefore, the AXA box contributes to increase Rab binding affinity to GDI upon complex formation.
-Finally, there is a highly conserved region in the CCR (residues 225-228) named the mobile effector loop (MEL). This part of the CCR directs GDI to the membrane and regulated the ability of GDI to retrieve Rab to the cytosol.
+Finally, there is a highly conserved region in the CCR (residues 225-228) named the <scene name='Sandbox_208/Residues_225-228_ccr/1'>mobile effector loop (MEL)</scene>. This part of the CCR directs GDI to the membrane and regulated the ability of GDI to retrieve Rab to the cytosol.
 *'''Domain II of GDI or Lipid Binding Site''': Domain II is rich in α helices. Helices D, E and H form a prenyl lipid binding pocket. Lys145 may play an important role in the lipid-binding cavity formation by functioning a spreader that keeps separated helices D and E. The GDI lipid binding pocket can adopt two different conformations, one being the open form when a lipid bound and the other being closed when neither lipid nor Rab is bound. A well ordered hydrophobic core stabilizes α helices D, E, F, G an H in a tighly packed state. This corresponds to the closed conformations of the GDI lipid binding site.