4ZYN
Crystal Structure of Parkin E3 ubiquitin ligase (linker deletion; delta 86-130)
Summary for 4ZYN
| Entry DOI | 10.2210/pdb4zyn/pdb |
| Related | 2ZEQ 4BM9 4I1H 4K7D 4K95 |
| Descriptor | E3 ubiquitin-protein ligase parkin, ZINC ION, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | ring domains, ubiquitin-like domain, rbr, ligase |
| Biological source | Rattus norvegicus (Rat) |
| Total number of polymer chains | 2 |
| Total formula weight | 96290.64 |
| Authors | Lilov, A.,Sauve, V.,Trempe, J.F.,Rodionov, D.,Wang, J.,Gehring, K. (deposition date: 2015-05-21, release date: 2015-08-19, Last modification date: 2023-09-27) |
| Primary citation | Sauve, V.,Lilov, A.,Seirafi, M.,Vranas, M.,Rasool, S.,Kozlov, G.,Sprules, T.,Wang, J.,Trempe, J.F.,Gehring, K. A Ubl/ubiquitin switch in the activation of Parkin. Embo J., 34:2492-2505, 2015 Cited by PubMed Abstract: Mutations in Parkin and PINK1 cause an inherited early-onset form of Parkinson's disease. The two proteins function together in a mitochondrial quality control pathway whereby PINK1 accumulates on damaged mitochondria and activates Parkin to induce mitophagy. How PINK1 kinase activity releases the auto-inhibited ubiquitin ligase activity of Parkin remains unclear. Here, we identify a binding switch between phospho-ubiquitin (pUb) and the ubiquitin-like domain (Ubl) of Parkin as a key element. By mutagenesis and SAXS, we show that pUb binds to RING1 of Parkin at a site formed by His302 and Arg305. pUb binding promotes disengagement of the Ubl from RING1 and subsequent Parkin phosphorylation. A crystal structure of Parkin Δ86-130 at 2.54 Å resolution allowed the design of mutations that specifically release the Ubl domain from RING1. These mutations mimic pUb binding and promote Parkin phosphorylation. Measurements of the E2 ubiquitin-conjugating enzyme UbcH7 binding to Parkin and Parkin E3 ligase activity suggest that Parkin phosphorylation regulates E3 ligase activity downstream of pUb binding. PubMed: 26254305DOI: 10.15252/embj.201592237 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.54 Å) |
Structure validation
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