6WCW

Structure of human Rubicon RH domain in complex with GTP-bound Rab7

Summary for 6WCW

• Entry DOI: 10.2210/pdb6wcw/pdb
• Descriptor: Ras-related protein Rab-7a, Run domain Beclin-1-interacting and cysteine-rich domain-containing protein, GUANOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: autophagy, rab, gtpase, aging, zinc finger, g protein, metal binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 51191.26

Authors

Bhargava, H.K.,Byck, J.M.,Farrell, D.P.,Anishchenko, I.,DiMaio, F.,Im, Y.J.,Hurley, J.H. (deposition date: 2020-03-31, release date: 2020-07-01, Last modification date: 2023-10-18)

Primary citation

Bhargava, H.K.,Tabata, K.,Byck, J.M.,Hamasaki, M.,Farrell, D.P.,Anishchenko, I.,DiMaio, F.,Im, Y.J.,Yoshimori, T.,Hurley, J.H.
Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex.
Proc.Natl.Acad.Sci.USA, 117:17003-17010, 2020

PubMed Abstract: Rubicon is a potent negative regulator of autophagy and a potential target for autophagy-inducing therapeutics. Rubicon-mediated inhibition of autophagy requires the interaction of the C-terminal Rubicon homology (RH) domain of Rubicon with Rab7-GTP. Here we report the 2.8-Å crystal structure of the Rubicon RH domain in complex with Rab7-GTP. Our structure reveals a fold for the RH domain built around four zinc clusters. The switch regions of Rab7 insert into pockets on the surface of the RH domain in a mode that is distinct from those of other Rab-effector complexes. Rubicon residues at the dimer interface are required for Rubicon and Rab7 to colocalize in living cells. Mutation of Rubicon RH residues in the Rab7-binding site restores efficient autophagic flux in the presence of overexpressed Rubicon, validating the Rubicon RH domain as a promising therapeutic target.

PubMed: 32632011
DOI: 10.1073/pnas.2008030117

Experimental method

X-RAY DIFFRACTION (2.8 Å)