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

Citation:
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.
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)
1
Histone-lysine N-methyltransferase Setd2(Gene symbol: SETD2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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