The structure of human neuronal Rab6B in the active and inactive form.
The Rab small G-protein family plays important roles in eukaryotes as regulators of vesicle traffic. In Rab proteins, the hydrolysis of GTP to GDP is coupled with association with and dissociation from membranes. Conformational changes related to their different nucleotide states determine their effector specificity. The crystal structure of human neuronal Rab6B was solved in its 'inactive' (with bound MgGDP) and 'active' (MgGTPgammaS-bound) forms to 2.3 and 1.8 A, respectively. Both crystallized in space group P2(1)2(1)2(1), with similar unit-cell parameters, allowing the comparison of both structures without packing artifacts. Conformational changes between the inactive GDP and active GTP-like state are observed mainly in the switch I and switch II regions, confirming their role as a molecular switch. Compared with other Rab proteins, additional changes are observed in the Rab6 subfamily-specific RabSF3 region that might contribute to the specificity of Rab6 for its different effector proteins.
Garcia-Saez
Isabel
I
Laboratoire des Moteurs Moléculaires (LMM), Institut de Biologie Structurale (CEA-CNRS-UJF), 41 Rue Jules Horowitz, 38027 Grenoble CEDEX 01, France.
Tcherniuk
Sergey
S
Kozielski
Frank
F
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002384:Catalysis; D018360:Crystallography, X-Ray / Q000379:methods; D004789:Enzyme Activation; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism*; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D020691:rab GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
C094135:Rab6 protein; D006153:Guanosine Diphosphate; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D020691:rab GTP-Binding Proteins; D008274:Magnesium