title: Structural basis for recruitment of Rab6-interacting protein 1 to Golgi via a RUN domain.
abstract: Small GTPase Rab6 regulates vesicle trafficking at the level of Golgi via recruitment of numerous and unrelated effectors. The crystal structure of Rab6a(GTP) in complex with a 378-residue internal fragment of the effector Rab6IP1 was solved at 3.2 angstroms resolution. This Rab6IP1 region encompasses an all alpha-helical RUN domain followed in tandem by a PLAT domain that adopts a beta sandwich fold. The structure reveals that the first and last alpha helices of the RUN domain mediate binding to switch I, switch II, and the interswitch region of Rab6. It represents the largest Rab-effector complex determined to date. Comparisons with the recent structure of Rab6 in complex with an unrelated effector, human golgin GCC185, reveals significant conformational changes in the conserved hydrophobic triad of Rab6. Flexibility in the switch and interswitch regions of Rab6 mediates recognition of compositionally distinct alpha-helical coiled coils, thereby contributing to Rab6 promiscuity in effector recruitment.
authors.affiliation: School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland.
authors.forename: Rosario
authors.initials: R
authors.lastname: Recacha
authors.forename: Annick
authors.initials: A
authors.lastname: Boulet
authors.forename: Florence
authors.initials: F
authors.lastname: Jollivet
authors.forename: Solange
authors.initials: S
authors.lastname: Monier
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: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers; D006056:Golgi Apparatus / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers