6if3

Publication Abstract from PubMed

Rab35, a master regulator of membrane trafficking, regulates diverse cellular processes and is associated with various human diseases. Although a number of effectors have been identified, the molecular basis of Rab35-effector interactions remains unclear. Here, we provide the high-resolution crystal structures of Rab35 in complex with its two specific effectors ACAP2 and RUSC2, respectively. In the Rab35/ACAP2 complex structure, Rab35 binds to the terminal ankyrin repeat and a C-terminal extended alpha helix of ACAP2, revealing a previously uncharacterized binding mode both for Rabs and ankyrin repeats. In the Rab35/RUSC2 complex structure, Arg1015 of RUSC2 functions as a "pseudo-arginine finger" that stabilizes the GTP-bound Rab35, thus facilitating the assembly of Rab35/RUSC2 complex. The structural analysis allows us to design specific Rab35 mutants capable of eliminating Rab35/ACAP2 and Rab35/RUSC2 interactions, but not interfering with other effector bindings. The atomic structures also offer possible explanations to disease-associated mutants identified at the Rab35-effector interfaces.

Rab35/ACAP2 and Rab35/RUSC2 Complex Structures Reveal Molecular Basis for Effector Recognition by Rab35 GTPase.,Lin L, Shi Y, Wang M, Wang C, Zhu J, Zhang R Structure. 2019 Mar 11. pii: S0969-2126(19)30078-4. doi:, 10.1016/j.str.2019.02.008. PMID:30905672^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.