Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28968219.
- Also identified by DOI 10.7554/eLife.29154 and PMC identifier 5624781.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Rab GTPases, which are involved in intracellular trafficking pathways, have recently been reported to be ubiquitinated. However, the functions of ubiquitinated Rab proteins remain unexplored. Here we show that Rab5 is monoubiquitinated on K116, K140, and K165. Upon co-transfection with ubiquitin, Rab5 exhibited abnormalities in endosomal localization and EGF-induced EGF receptor degradation. Rab5 K140R and K165R mutants restored these abnormalities, whereas K116R did not. We derived structural models of individual monoubiquitinated Rab5 proteins (mUbRab5s) by solution scattering and observed different conformational flexibilities in a site-specific manner. Structural analysis combined with biochemical data revealed that interactions with downstream effectors were impeded in mUbRab5<sub>K140</sub>, whereas GDP release and GTP loading activities were altered in mUbRab5<sub>K165</sub>. By contrast, mUbRab5<sub>K116</sub> apparently had no effect. We propose a regulatory mechanism of Rab5 where monoubiquitination downregulates effector recruitment and GDP/GTP conversion in a site-specific manner.
Medical subject headings
- Down-Regulation
- Guanine Nucleotides
- Ubiquitination
- rab5 GTP-Binding Proteins