 |
PDBsum entry 2mdj
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Autoinhibitory structure of the ww domain of hypb/setd2 regulates its interaction with the proline-Rich region of huntingtin.
|
|
|
Authors
|
|
Y.G.Gao,
H.Yang,
J.Zhao,
Y.J.Jiang,
H.Y.Hu.
|
|
|
Ref.
|
|
Structure, 2014,
22,
378-386.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
