Structural basis for recruitment of traffic proteins by small GTPases

Abstract

Vesicular trafficking plays significant roles in exocytosis, endocytosis and cell component recycling. Small GTPases are involved in all stages of vesicular trafficking by recruiting their effectors. In the thesis I present two protein complex structures, Arl1-GRIP domain and Rab7-RILP effector domain complexes, to elucidate the molecular mechanism by which Arl1 and Rab7 recruit their respective effectors by X-ray crystallography. The structure of the Arl1-GRIP domain complex showed that the GRIP domain forms a tight homodimer. Switch II region of Arl1 confers to the specificity of binding to GRIP domain. Functional studies on the GRIP domain strongly suggest that the dimeric form of the GRIP domain is a functional unit. In Rab7-RILP effector domain structure, both the switch regions and the hypervariable regions (RabSF1 and RabSF4) of Rab7 are involved in the interaction with RILP. Site-directed mutagenesis on RILP suggests that RILP functions as a dimer in cells.