3ECW

Crystal structure of the ALS-related pathological mutant T54R of human apo Cu,Zn Superoxide Dismutase (SOD1)

3ECW の概要

• エントリーDOI: 10.2210/pdb3ecw/pdb
• 関連するPDBエントリー: 3ECU 3ECV
• 分子名称: Superoxide dismutase [Cu-Zn] (2 entities in total)
• 機能のキーワード: human superoxide dismutase, homodimeric protein, apo protein, aggregation, als, mutant, acetylation, amyotrophic lateral sclerosis, antioxidant, copper, cytoplasm, disease mutation, metal-binding, oxidoreductase, ubl conjugation, zinc
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: P00441
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 63534.60

構造登録者

Calderone, V. (登録日: 2008-09-02, 公開日: 2009-05-19, 最終更新日: 2024-11-06)

主引用文献

Banci, L.,Bertini, I.,Boca, M.,Calderone, V.,Cantini, F.,Girotto, S.,Vieru, M.
Structural and dynamic aspects related to oligomerization of apo SOD1 and its mutants.
Proc.Natl.Acad.Sci.USA, 106:6980-6985, 2009

PubMed Abstract: The structural and dynamical properties of the metal-free form of WT human superoxide dismutase 1 (SOD1) and its familial amyotrophic lateral sclerosis (fALS)-related mutants, T54R and I113T, were characterized both in solution, through NMR, and in the crystal, through X-ray diffraction. We found that all 3 X-ray structures show significant structural disorder in 2 loop regions that are, at variance, well defined in the fully-metalated structures. Interestingly, the apo state crystallizes only at low temperatures, whereas all 3 proteins in the metalated form crystallize at any temperature, suggesting that crystallization selects one of the most stable conformations among the manifold adopted by the apo form in solution. Indeed, NMR experiments show that the protein in solution is highly disordered, sampling a large range of conformations. The large conformational variability of the apo state allows the free reduced cysteine Cys-6 to become highly solvent accessible in solution, whereas it is essentially buried in the metalated state and the crystal structures. Such solvent accessibility, together with that of Cys-111, accounts for the tendency to oligomerization of the metal-free state. The present results suggest that the investigation of the solution state coupled with that of the crystal state can provide major insights into SOD1 pathway toward oligomerization in relation to fALS.

PubMed: 19369197
DOI: 10.1073/pnas.0809845106

実験手法

X-RAY DIFFRACTION (2.15 Å)