Structural Insights into the Specific Binding of Huntingtin Proline-Rich Region with the SH3 and WW Domains

Yong Guang Gao, Xian Zhong Yan, Ai Xin Song, Yong Gang Chang, Xue Chao Gao, Nan Jiang, Qi Zhang, Hong Yu Hu

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

Abstract

The interactions of huntingtin (Htt) with the SH3 domain- or WW domain-containing proteins have been implicated in the pathogenesis of Huntington's disease (HD). We report the specific interactions of Htt proline-rich region (PRR) with the SH3GL3-SH3 domain and HYPA-WW1-2 domain pair by NMR. The results show that Htt PRR binds with the SH3 domain through nearly its entire chain, and that the binding region on the domain includes the canonical PxxP-binding site and the specificity pocket. The C terminus of PRR orients to the specificity pocket, whereas the N terminus orients to the PxxP-binding site. Htt PRR can also specifically bind to WW1-2; the N-terminal portion preferentially binds to WW1, while the C-terminal portion binds to WW2. This study provides structural insights into the specific interactions between Htt PRR and its binding partners as well as the alteration of these interactions that involve PRR, which may have implications for the understanding of HD.

Original languageEnglish
Pages (from-to)1755-1765
Number of pages11
JournalStructure
Volume14
Issue number12
DOIs
Publication statusPublished - Dec 2006
Externally publishedYes

Keywords

  • MOLNEURO
  • PROTEINS

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