2MDI: Solution structure of the PP2WW mutant (KPP2WW) of HYPB

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.
PDB ID: 2MDIDownload
MMDB ID: 122963
PDB Deposition Date: 2013/9/10
Updated in MMDB: 2014/09
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 2MDI: monomeric; determined by author
Molecular Components in 2MDI
Label Count Molecule
Protein (1 molecule)
Histone-lysine N-methyltransferase Setd2(Gene symbol: SETD2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB