Unknown

Dataset Information

0

Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex.


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.

SUBMITTER: Bhargava HK 

PROVIDER: S-EPMC7382272 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC2984168 | biostudies-literature
| S-EPMC8458453 | biostudies-literature
| S-EPMC6363164 | biostudies-literature
| S-EPMC4853476 | biostudies-literature
| S-EPMC1142575 | biostudies-literature
| S-EPMC9335260 | biostudies-literature
| S-EPMC9935631 | biostudies-literature
| S-EPMC6888122 | biostudies-literature
| S-EPMC7614227 | biostudies-literature
| S-EPMC8501788 | biostudies-literature