期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 284, 期 5, 页码 2628-2635出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M806003200
关键词
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资金
- DFG [AL 484/7-2]
- SFB [642]
Rab GTPases are key regulators of intracellular vesicular transport that control vesicle budding, cargo sorting, transport, tethering, and fusion. In the inactive (GDP-bound) conformation, Rab GTPases are targeted to intracellular compartments where they are converted into the active GTP-bound form and recruit effector domain containing proteins. Rab6a has been implicated in dynein-mediated vesicle movement at the Golgi apparatus and shown to interact with a plethora of effector proteins. In this study, we identify minimal Rab6a binding domains of three Rab6a effector proteins: PIST, BicaudalD2, and p150(glued). All three domains are >15-kDa fragments predicted to form coiled-coil structures that display no sequence homology to each other. Complex formation with BicaudalD2 and p150 has a moderate inhibitory effect on the intrinsic GTPase activity of Rab6a, while interaction with PIST has no influence on the hydrolysis rate. The effectors bind activated Rab6a with comparable affinities with K-d values ranging from high nanomolar to low micromolar. Transient kinetic analysis revealed that effectors bind to Rab6a in an apparent single-step reaction characterized by relatively rapid on- and off-rates. We propose that the high off-rates of Rab6.effector complexes enable GTPase-activating protein-mediated net dissociation, which would not be possible if the off-rate were significantly slower.
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