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.
|
Authors | Yong-Guang Gao, Hui Yang, Jian Zhao, Ya-Jun Jiang, Hong-Yu Hu |
Journal | Structure (London, England : 1993)
(Structure)
Vol. 22
Issue 3
Pg. 378-86
(Mar 04 2014)
ISSN: 1878-4186 [Electronic] United States |
PMID | 24412394
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- HTT protein, human
- Huntingtin Protein
- Nerve Tissue Proteins
- Peptides
- polyproline
- Histone-Lysine N-Methyltransferase
- SETD2 protein, human
|
Topics |
- Amino Acid Sequence
- Binding Sites
- Histone-Lysine N-Methyltransferase
(chemistry, genetics, metabolism)
- Humans
- Huntingtin Protein
- Magnetic Resonance Spectroscopy
- Models, Molecular
- Molecular Sequence Data
- Mutation
- Nerve Tissue Proteins
(chemistry, metabolism)
- Peptides
- Protein Conformation
- Protein Structure, Tertiary
|