3QQD

Human SOD1 H80R variant, P212121 crystal form

「3H2R」から置き換えられました

3QQD の概要

• エントリーDOI: 10.2210/pdb3qqd/pdb
• 関連するPDBエントリー: 3H2P 3H2Q
• 分子名称: Superoxide dismutase [Cu-Zn], ZINC ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: oxidoreductase, human cu, zn superoxide dismutase, antioxidant, metal-binding, amyotrophic lateral sclerosis, disease mutation, disulfide bond
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P00441 P00441
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32132.24

構造登録者

Seetharaman, S.V.,Winkler, D.D.,Taylor, A.B.,Cao, X.,Whitson, L.J.,Doucette, P.A.,Valentine, J.S.,Schirf, V.,Demeler, B.,Carroll, M.C.,Culotta, V.C.,Hart, P.J. (登録日: 2011-02-15, 公開日: 2011-03-09, 最終更新日: 2023-12-06)

主引用文献

Seetharaman, S.V.,Winkler, D.D.,Taylor, A.B.,Cao, X.,Whitson, L.J.,Doucette, P.A.,Valentine, J.S.,Schirf, V.,Demeler, B.,Carroll, M.C.,Culotta, V.C.,Hart, P.J.
Disrupted zinc-binding sites in structures of pathogenic SOD1 variants D124V and H80R.
Biochemistry, 49:5714-5725, 2010

PubMed Abstract: Mutations in human copper-zinc superoxide dismutase (SOD1) cause an inherited form of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS). Here, we present structures of the pathogenic SOD1 variants D124V and H80R, both of which demonstrate compromised zinc-binding sites. The disruption of the zinc-binding sites in H80R SOD1 leads to conformational changes in loop elements, permitting non-native SOD1-SOD1 interactions that mediate the assembly of these proteins into higher-order filamentous arrays. Analytical ultracentrifugation sedimentation velocity experiments indicate that these SOD1 variants are more prone to monomerization than the wild-type enzyme. Although D124V and H80R SOD1 proteins appear to have fully functional copper-binding sites, inductively coupled plasma mass spectrometery (ICP-MS) and anomalous scattering X-ray diffraction analyses reveal that zinc (not copper) occupies the copper-binding sites in these variants. The absence of copper in these proteins, together with the results of covalent thiol modification experiments in yeast strains with and without the gene encoding the copper chaperone for SOD1 (CCS), suggests that CCS may not fully act on newly translated forms of these polypeptides. Overall, these findings lend support to the hypothesis that immature mutant SOD1 species contribute to toxicity in SOD1-linked ALS.

PubMed: 20515040
DOI: 10.1021/bi100314n

実験手法

X-RAY DIFFRACTION (1.653 Å)