6IF3

Complex structure of Rab35 and its effector ACAP2

Summary for 6IF3

• Entry DOI: 10.2210/pdb6if3/pdb
• Descriptor: Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2, Ras-related protein Rab-35, GUANOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: rab35, acap2, complex, cryatal structure, endocytosis
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 40643.49

Authors

Lin, L.,Zhu, J.,Zhang, R. (deposition date: 2018-09-18, release date: 2019-04-03, Last modification date: 2023-11-22)

Primary citation

Lin, L.,Shi, Y.,Wang, M.,Wang, C.,Zhu, J.,Zhang, R.
Rab35/ACAP2 and Rab35/RUSC2 Complex Structures Reveal Molecular Basis for Effector Recognition by Rab35 GTPase.
Structure, 27:729-, 2019

PubMed Abstract: 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 α 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.

PubMed: 30905672
DOI: 10.1016/j.str.2019.02.008

Experimental method

X-RAY DIFFRACTION (1.5 Å)