Article

Structural basis for recruitment of Rab6-interacting protein 1 to Golgi via a RUN domain.

School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland.
Structure (impact factor: 6.35). 02/2009; 17(1):21-30. DOI:10.1016/j.str.2008.10.014
Source: PubMed

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.

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Keywords

3.2 angstroms resolution
 
alpha-helical RUN domain
 
compositionally distinct alpha-helical coiled coils
 
conserved hydrophobic triad
 
crystal structure
 
effector Rab6IP1
 
Golgi
 
human golgin GCC185
 
interswitch region
 
interswitch regions
 
largest Rab-effector complex
 
last alpha helices
 
numerous
 
PLAT domain
 
Rab6 mediates recognition
 
Rab6 promiscuity
 
Rab6IP1 region encompasses
 
recent structure
 
significant conformational changes
 
Small GTPase Rab6 regulates vesicle trafficking