RAB6 Interacting Protein 1 (RAB6IP1)

Rab6 regulates vesicular cargo at the level of Golgi via interactions with numerous and unrelated effector proteins. The crystal structure of Rab6a(GTP) in complex with a 378-residue internal fragment of the effector Rab6IP1 (Rab6 Interacting Protein 1) has been solved at 3.2Å resolution. This region of Rab6IP1 encompasses an all a -helical RUN domain followed in tandem by a PLAT domain that adopts a b -sandwich fold. The structure reveals that the first and last a -helices of the RUN domain mediate binding to switch I, switch II and the interswitch region of Rab6. The structure represents the largest Rab-effector complex determined to date. Comparisons to the recent structure of Rab6 in complex with an unrelated effector, human golgin GCC185 (ref), reveals significant conformational changes in the conserved hydrophobic triad of Rab6.