3O10

Crystal structure of the HEPN domain from human sacsin

3O10 の概要

• エントリーDOI: 10.2210/pdb3o10/pdb
• 分子名称: Sacsin, MALONATE ION (3 entities in total)
• 機能のキーワード: all-helical domain, homodimerization, chaperone
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q9NZJ4
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 64934.13

構造登録者

Kozlov, G.,Gehring, K. (登録日: 2010-07-20, 公開日: 2011-03-30, 最終更新日: 2024-11-27)

主引用文献

Kozlov, G.,Denisov, A.Y.,Girard, M.,Dicaire, M.J.,Hamlin, J.,McPherson, P.S.,Brais, B.,Gehring, K.
Structural basis of defects in the sacsin HEPN domain responsible for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).
J.Biol.Chem., 286:20407-20412, 2011

PubMed Abstract: Sacsin is a 520-kDa protein mutated in the early-onset neurodevelopmental and neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The C terminus of the protein contains an HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain of unknown function. Here, we determined the high-resolution 1.9-Å crystal structure of the HEPN domain from human sacsin. The structure is composed of five parallel α-helices with a large loop of several short helical segments. Two HEPN protomers assemble as a dimer to form a large positively charged cavity at the dimer interface that binds GTP and other nucleotides. The crystal structure reveals that the ARSACS N4549D mutation disrupts dimerization and protein folding. This study provides novel insights into the oligomerization state of sacsin and functions that are lost in mutations that cause ARSACS.

PubMed: 21507954
DOI: 10.1074/jbc.M111.232884

実験手法

X-RAY DIFFRACTION (1.9 Å)