title: Structural aspects of Rab6-effector complexes.
abstract: The small GTPase Rab6 regulates vesicle trafficking at the level of Golgi. Recently, the crystal structures of Rab6 in complexes with two unrelated effectors have been determined. The structure of Rab6a-GTP in complex with a 378-residue internal fragment of the effector Rab6IP1 (Rab6-interacting protein 1) has been solved. In addition, the structure of Rab6 with the golgin, GCC185, has also been determined. In both complexes, two alpha-helices from the effector mediate binding to switch I, switch II and the interswitch region of Rab6. Comparisons of the complexes reveal significant conformational changes in the conserved hydrophobic triad of Rab6. Thus conformational flexibility in the triad mediates recognition of compositionally distinct alpha-helical coiled coils, providing a rationale for the promiscuity of Rab6 in effector recruitment.
authors.affiliation: School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland.
authors.forename: Humberto
authors.initials: H
authors.lastname: Fernandes
authors.forename: Edward
authors.initials: E
authors.lastname: Franklin
authors.forename: Rosario
authors.initials: R
authors.lastname: Recacha
authors.forename: Anne
authors.initials: A
authors.lastname: Houdusse
authors.forename: Bruno
authors.initials: B
authors.lastname: Goud
authors.forename: Amir R
authors.initials: AR
authors.lastname: Khan
mesh_terms: D006056:Golgi Apparatus / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry; D011487:Protein Conformation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D020691:rab GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C574860:DENND5A protein, human; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D020033:Protein Isoforms; C094135:Rab6 protein; D020691:rab GTP-Binding Proteins