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Updated: Dec 15, 2025

Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex
Hersh K Bhargava1,2, Keisuke Tabata3, Jordan M Byck1,2
1Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
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.
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