3CQP

Human SOD1 G85R Variant, Structure I

Summary for 3CQP

• Entry DOI: 10.2210/pdb3cqp/pdb
• Related: 3CQQ
• Descriptor: Superoxide dismutase [Cu-Zn], COPPER (II) ION, ZINC ION, ... (5 entities in total)
• Functional Keywords: oxidoreductase, human cu, zn superoxide dismutase, antioxidant, metal-binding, amyotrophic lateral sclerosis, disease mutation
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P00441
• Total number of polymer chains: 4
• Total formula weight: 64365.31

Authors

Cao, X.,Antonyuk, S.,Seetharaman, S.V.,Whitson, L.J.,Taylor, A.B.,Holloway, S.P.,Strange, R.W.,Doucette, P.A.,Valentine, J.S.,Tiwari, A.,Hayward, L.J.,Padua, S.,Cohlberg, J.A.,Hasnain, S.S.,Hart, P.J. (deposition date: 2008-04-03, release date: 2008-04-29, Last modification date: 2023-08-30)

Primary citation

Cao, X.,Antonyuk, S.V.,Seetharaman, S.V.,Whitson, L.J.,Taylor, A.B.,Holloway, S.P.,Strange, R.W.,Doucette, P.A.,Valentine, J.S.,Tiwari, A.,Hayward, L.J.,Padua, S.,Cohlberg, J.A.,Hasnain, S.S.,Hart, P.J.
Structures of the G85R Variant of SOD1 in Familial Amyotrophic Lateral Sclerosis.
J.Biol.Chem., 283:16169-16177, 2008

PubMed Abstract: Mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause a dominant form of the progressive neurodegenerative disease amyotrophic lateral sclerosis. Transgenic mice expressing the human G85R SOD1 variant develop paralytic symptoms concomitant with the appearance of SOD1-enriched proteinaceous inclusions in their neural tissues. The process(es) through which misfolding or aggregation of G85R SOD1 induces motor neuron toxicity is not understood. Here we present structures of the human G85R SOD1 variant determined by single crystal x-ray diffraction. Alterations in structure of the metal-binding loop elements relative to the wild type enzyme suggest a molecular basis for the metal ion deficiency of the G85R SOD1 protein observed in the central nervous system of transgenic mice and in purified recombinant G85R SOD1. These findings support the notion that metal-deficient and/or disulfide-reduced mutant SOD1 species contribute to toxicity in SOD1-linked amyotrophic lateral sclerosis.

PubMed: 18378676
DOI: 10.1074/jbc.M801522200

Experimental method

X-RAY DIFFRACTION (1.95 Å)