3ECW

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

Summary for 3ECW

• Entry DOI: 10.2210/pdb3ecw/pdb
• Related: 3ECU 3ECV
• Descriptor: Superoxide dismutase [Cu-Zn] (2 entities in total)
• Functional Keywords: 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
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: P00441
• Total number of polymer chains: 4
• Total formula weight: 63534.60

Authors

Calderone, V. (deposition date: 2008-09-02, release date: 2009-05-19, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.15 Å)