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How does monoubiquitin turn down Rab5?

Rab5 is monoubiquitinated at specific lysines; ubiquitin at K140/K165 disrupts effector binding and downregulates endocytic trafficking.

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At which lysines is Rab5 monoubiquitinated?

K116, K140, and K165 in HEK 293T and HeLa cells.

Source: Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion · DOI · quote verified

What cellular process does Rab5 regulate?

Formation of early endosomes and maturation to late endosomes.

Source: Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion · DOI · quote verified

How does monoubiquitination at K140/K165 affect the pathway?

It downregulates the Rab5-mediated endocytic pathway.

Source: Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion · DOI · quote verified

Is K116 monoubiquitination critical for localization downregulation?

No—K116 monoubiquitination has no apparent effect on that downregulation.

Source: Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion · DOI · quote verified

What happens to mUbRab5 K165 nucleotide handling?

Reduced GDP release and weakened GTP loading.

Source: Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion · DOI · quote verified

Why test effector binding after monoubiquitination?

Ubiquitin may sterically clash with Rab5 partners such as GEF/GAP/effectors.

Source: Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion · DOI · quote verified

What experimental systems mapped the sites?

Ubiquitination assays in HEK 293T and HeLa cells.

Source: Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion · DOI · quote verified

What open question remains about the E3?

The E3 ligase that monoubiquitinates Rab5 is not yet identified here.

Source: Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion · DOI · quote verified

What structural approach modeled mUbRab5?

Solution scattering ensemble models of monoubiquitinated Rab5.

Source: Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion · DOI · quote verified

What is the paper’s trafficking takeaway?

Site-specific monoubiquitin is an inhibitory signal on Rab5 endocytosis.

Source: Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion · DOI · quote verified

Which Rab5 partners were considered in complex models?

Rabex-5 (GEF), RabGAP-5 (GAP), and Rabaptin5.

Source: Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion · DOI · quote verified