1YZB
Solution structure of the Josephin domain of Ataxin-3
Summary for 1YZB
| Entry DOI | 10.2210/pdb1yzb/pdb |
| NMR Information | BMRB: 6241 |
| Descriptor | Machado-Joseph disease protein 1 (1 entity in total) |
| Functional Keywords | papain-like fold, transcription |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus matrix: P54252 |
| Total number of polymer chains | 1 |
| Total formula weight | 21053.77 |
| Authors | Nicastro, G.,Masino, L.,Menon, R.P.,Knowles, P.P.,McDonald, N.Q.,Pastore, A. (deposition date: 2005-02-28, release date: 2005-07-05, Last modification date: 2024-05-29) |
| Primary citation | Nicastro, G.,Menon, R.P.,Masino, L.,Knowles, P.P.,McDonald, N.Q.,Pastore, A. The solution structure of the Josephin domain of ataxin-3: Structural determinants for molecular recognition Proc.Natl.Acad.Sci.Usa, 102:10493-10498, 2005 Cited by PubMed Abstract: The Josephin domain plays an important role in the cellular functions of ataxin-3, the protein responsible for the neurodegenerative Machado-Joseph disease. We have determined the solution structure of Josephin and shown that it belongs to the family of papain-like cysteine proteases, sharing the highest degree of structural similarity with bacterial staphopain. A currently unique structural feature of Josephin is a flexible helical hairpin formed by a 32-residue insertion, which could determine substrate specificity. By using the Josephin structure and the availability of NMR chemical shift assignments, we have mapped the enzyme active site by using the typical cysteine protease inhibitors, transepoxysuccinyl-L-eucylamido-4-guanidino-butane (E-64) and [L-3-trans-(propylcarbamyl)oxirane-2-carbonyl]-L-isoleucyl-L-proline (CA-074). We also demonstrate that the specific interaction of Josephin with the ubiquitin-like domain of the ubiquitin- and proteasome-binding factor HHR23B involves complementary exposed hydrophobic surfaces. The structural similarity with other deubiquitinating enzymes suggests a model for the proteolytic enzymatic activity of ataxin-3. PubMed: 16020535DOI: 10.1073/pnas.0501732102 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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