2M6N
3D solution structure of EMI1 (Early Mitotic Inhibitor 1)
Summary for 2M6N
| Entry DOI | 10.2210/pdb2m6n/pdb |
| Related | 2CT7 2JMO |
| NMR Information | BMRB: 19147 |
| Descriptor | F-box only protein 5, ZINC ION (2 entities in total) |
| Functional Keywords | emi1, apc, e3 ligase, zbr, cell cycle |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus: Q9UKT4 |
| Total number of polymer chains | 1 |
| Total formula weight | 9736.18 |
| Authors | Frye, J.J.,Brown, N.G.,Petzold, G.,Watson, E.R.,Royappa, G.R.,Nourse, A.,Jarvis, M.,Kriwacki, R.W.,Peters, J.,Stark, H.,Schulman, B.A. (deposition date: 2013-04-06, release date: 2013-05-29, Last modification date: 2024-05-01) |
| Primary citation | Frye, J.J.,Brown, N.G.,Petzold, G.,Watson, E.R.,Grace, C.R.,Nourse, A.,Jarvis, M.A.,Kriwacki, R.W.,Peters, J.M.,Stark, H.,Schulman, B.A. Electron microscopy structure of human APC/C(CDH1)-EMI1 reveals multimodal mechanism of E3 ligase shutdown. Nat.Struct.Mol.Biol., 20:827-835, 2013 Cited by PubMed Abstract: The anaphase-promoting complex/cyclosome (APC/C) is a ~1.5-MDa multiprotein E3 ligase enzyme that regulates cell division by promoting timely ubiquitin-mediated proteolysis of key cell-cycle regulatory proteins. Inhibition of human APC/C(CDH1) during interphase by early mitotic inhibitor 1 (EMI1) is essential for accurate coordination of DNA synthesis and mitosis. Here, we report a hybrid structural approach involving NMR, electron microscopy and enzymology, which reveal that EMI1's 143-residue C-terminal domain inhibits multiple APC/C(CDH1) functions. The intrinsically disordered D-box, linker and tail elements, together with a structured zinc-binding domain, bind distinct regions of APC/C(CDH1) to synergistically both block the substrate-binding site and inhibit ubiquitin-chain elongation. The functional importance of intrinsic structural disorder is explained by enabling a small inhibitory domain to bind multiple sites to shut down various functions of a 'molecular machine' nearly 100 times its size. PubMed: 23708605DOI: 10.1038/nsmb.2593 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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