2MDJ
Solution structure of WW domain with polyproline stretch (PP2WW) of HYPB
Summary for 2MDJ
| Entry DOI | 10.2210/pdb2mdj/pdb |
| Related | 2MDC 2MDI |
| NMR Information | BMRB: 19488 |
| Descriptor | Histone-lysine N-methyltransferase SETD2 (1 entity in total) |
| Functional Keywords | ww domain, hypb, polyproline, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus (Probable): Q9BYW2 |
| Total number of polymer chains | 1 |
| Total formula weight | 6336.02 |
| Authors | |
| Primary citation | Gao, Y.G.,Yang, H.,Zhao, J.,Jiang, Y.J.,Hu, H.Y. Autoinhibitory structure of the WW domain of HYPB/SETD2 regulates its interaction with the proline-rich region of huntingtin Structure, 22:378-386, 2014 Cited by PubMed Abstract: Huntington's disease (HD) is an autosomally dominant neurodegenerative disorder caused by expansion of polyglutamine (polyQ) in the huntingtin (Htt) protein. Htt yeast two-hybrid protein B (HYPB/SETD2), a histone methyltransferase, directly interacts with Htt and is involved in HD pathology. Using NMR techniques, we characterized a polyproline (polyP) stretch at the C terminus of HYPB, which directly interacts with the following WW domain and leads this domain predominantly to be in a closed conformational state. The solution structure shows that the polyP stretch extends from the back and binds to the WW core domain in a typical binding mode. This autoinhibitory structure regulates interaction between the WW domain of HYPB and the proline-rich region (PRR) of Htt, as evidenced by NMR and immunofluorescence techniques. This work provides structural and mechanistic insights into the intramolecular regulation of the WW domain in Htt-interacting partners and will be helpful for understanding the pathology of HD. PubMed: 24412394DOI: 10.1016/j.str.2013.12.005 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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