Mechanism of ubiquitylation by dimeric RING ligase RNF4
| Autor: | Kenneth A. Johnson, Ronald T. Hay, Stephen A. McMahon, Ellis Jaffray, Iva Navratilova, James H. Naismith, Anna Plechanovová |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Stereochemistry Recombinant Fusion Proteins Ubiquitin-Protein Ligases Dimer Ubiquitin-conjugating enzyme Biology Thioester Binding Competitive Article chemistry.chemical_compound Ubiquitin Structural Biology Catalytic Domain Animals Molecular Biology chemistry.chemical_classification DNA ligase RNF4 Ubiquitination Nuclear Proteins Protein Structure Tertiary Rats Ubiquitin ligase Monomer chemistry Biochemistry Ubiquitin-Conjugating Enzymes biology.protein RING Finger Domains Dimerization Transcription Factors |
| Zdroj: | Nature Structural & Molecular Biology. 18:1052-1059 |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | Mammalian RNF4 is a dimeric RING ubiquitin E3 ligase that ubiquitylates poly-SUMOylated proteins. We found that RNF4 bound ubiquitin-charged UbcH5a tightly but free UbcH5a weakly. To provide insight into the mechanism of RING-mediated ubiquitylation, we docked the UbcH5~ubiquitin thioester onto the RNF4 RING structure. This revealed that with E2 bound to one monomer of RNF4, the thioester-linked ubiquitin could reach across the dimer to engage the other monomer. In this model, the 'Ile44 hydrophobic patch' of ubiquitin is predicted to engage a conserved tyrosine located at the dimer interface of the RING, and mutation of these residues blocked ubiquitylation activity. Thus, dimeric RING ligases are not simply inert scaffolds that bring substrate and E2-loaded ubiquitin into close proximity. Instead, they facilitate ubiquitin transfer by preferentially binding the E2~ubiquitin thioester across the dimer and activating the thioester bond for catalysis. |
| Databáze: | OpenAIRE |
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