3IO6

Huntingtin amino-terminal region with 17 Gln residues - crystal C92-a

Summary for 3IO6

• Entry DOI: 10.2210/pdb3io6/pdb
• Related: 3IO4 3IOR 3IOT 3IOU 3IOV 3IOW
• Descriptor: Maltose-binding periplasmic protein, HUNTINGTIN FUSION PROTEIN, ZINC ION, CALCIUM ION (3 entities in total)
• Functional Keywords: huntingtin, htt-ex1, hd, sugar transport, transport, apoptosis, disease mutation, nucleus, phosphoprotein, signaling protein
• Biological source: Escherichia coli K-12, Homo sapiens (bacteria, human)
• Cellular location: Cytoplasm: P42858
• Total number of polymer chains: 3
• Total formula weight: 148637.89

Authors

Kim, M.W.,Chelliah, Y.,Kim, S.W.,Otwinowski, Z.,Bezprozvanny, I. (deposition date: 2009-08-13, release date: 2009-10-27, Last modification date: 2024-02-21)

Primary citation

Kim, M.W.,Chelliah, Y.,Kim, S.W.,Otwinowski, Z.,Bezprozvanny, I.
Secondary structure of Huntingtin amino-terminal region.
Structure, 17:1205-1212, 2009

PubMed Abstract: 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.

PubMed: 19748341
DOI: 10.1016/j.str.2009.08.002

Experimental method

X-RAY DIFFRACTION (3.7 Å)