6N13
UbcH7-Ub Complex with R0RBR Parkin and phosphoubiquitin
Summary for 6N13
| Entry DOI | 10.2210/pdb6n13/pdb |
| Related | 1UBQ 4Q5E 5N2W |
| NMR Information | BMRB: 27664 |
| Descriptor | E3 ubiquitin-protein ligase parkin, ubiquitin, Ubiquitin-conjugating enzyme E2 L3, ... (5 entities in total) |
| Functional Keywords | e3 enzyme, protein degradation, mitochondrial protein, ligase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 71885.83 |
| Authors | Condos, T.E.C.,Dunkerley, K.M.,Freeman, E.A.,Barber, K.R.,Aguirre, J.D.,Chaugule, V.K.,Xiao, Y.,Konermann, L.,Walden, H.,Shaw, G.S. (deposition date: 2018-11-08, release date: 2018-11-28, Last modification date: 2024-11-13) |
| Primary citation | Condos, T.E.,Dunkerley, K.M.,Freeman, E.A.,Barber, K.R.,Aguirre, J.D.,Chaugule, V.K.,Xiao, Y.,Konermann, L.,Walden, H.,Shaw, G.S. Synergistic recruitment of UbcH7~Ub and phosphorylated Ubl domain triggers parkin activation. EMBO J., 37:-, 2018 Cited by PubMed Abstract: The E3 ligase parkin ubiquitinates outer mitochondrial membrane proteins during oxidative stress and is linked to early-onset Parkinson's disease. Parkin is autoinhibited but is activated by the kinase PINK1 that phosphorylates ubiquitin leading to parkin recruitment, and stimulates phosphorylation of parkin's N-terminal ubiquitin-like (pUbl) domain. How these events alter the structure of parkin to allow recruitment of an E2~Ub conjugate and enhanced ubiquitination is an unresolved question. We present a model of an E2~Ub conjugate bound to the phospho-ubiquitin-loaded C-terminus of parkin, derived from NMR chemical shift perturbation experiments. We show the UbcH7~Ub conjugate binds in the open state whereby conjugated ubiquitin binds to the RING1/IBR interface. Further, NMR and mass spectrometry experiments indicate the RING0/RING2 interface is re-modelled, remote from the E2 binding site, and this alters the reactivity of the RING2(Rcat) catalytic cysteine, needed for ubiquitin transfer. Our experiments provide evidence that parkin phosphorylation and E2~Ub recruitment act synergistically to enhance a weak interaction of the pUbl domain with the RING0 domain and rearrange the location of the RING2(Rcat) domain to drive parkin activity. PubMed: 30446597DOI: 10.15252/embj.2018100014 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
