3IOR: Huntingtin Amino-terminal Region With 17 Gln Residues - Crystal C95

Huntington's disease is a genetic neurodegenerative disorder resulting from polyglutamine (polyQ) expansion (>36Q) within the first exon of Huntingtin (Htt) protein. We applied X-ray crystallography to determine the secondary structure of the first exon (EX1) of Htt17Q. The structure of Htt17Q-EX1 consists of an amino-terminal alpha helix, poly17Q region, and polyproline helix formed by the proline-rich region. The poly17Q region adopts multiple conformations in the structure, including alpha helix, random coil, and extended loop. The conformation of the poly17Q region is influenced by the conformation of neighboring protein regions, demonstrating the importance of the native protein context. We propose that the conformational flexibility of the polyQ region observed in our structure is a common characteristic of many amyloidogenic proteins. We further propose that the pathogenic polyQ expansion in the Htt protein increases the length of the random coil, which promotes aggregation and facilitates abnormal interactions with other proteins in cells.
PDB ID: 3IORDownload
MMDB ID: 77066
PDB Deposition Date: 2009/8/14
Updated in MMDB: 2009/09
Experimental Method:
x-ray diffraction
Resolution: 3.6  Å
Similar Structures:
Biological Unit for 3IOR: trimeric; determined by software (PISA)
Molecular Components in 3IOR
Label Count Molecule
Proteins (3 molecules)
Maltose-binding Protein, Huntingtin Fusion Protein
Molecule annotation
Chemicals (12 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB