期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 328, 期 4, 页码 877-891出版社
ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1016/S0022-2836(03)00355-3
关键词
Cu, Zn superoxide dismutase; familial amyotrophic lateral sclerosis; ALS; amyloid; SOD1
资金
- NIGMS NIH HHS [GM28222] Funding Source: Medline
- NINDS NIH HHS [NS44170, NS39112, R01 NS044170, R01 NS039112] Funding Source: Medline
Cu, Zn superoxide dismutase (SOD1) forms a crucial component of the cellular defence against oxidative stress. Zn-deficient wild-type and mutant human SOD1 have been implicated in the disease familial amyotrophic lateral sclerosis (FALS). We present here the crystal structures of holo and metal-deficient (apo) wild-type protein at 1.8 Angstrom resolution. The P21 wild-type holo enzyme structure has nine independently refined dimers and these combine to form a trimer of dimers packing motif in monomers in these dimers, in contrast to the subunit structures of the FALS G37R mutant of human SOD1 and in bovine Cu,Zn SOD. Metal-deficient apo SOD1 crystallizes with two dimers in the asymmetric unit and shows changes in the metal-binding sites and disorder in the Zn binding and electrostatic loops of one dimer, which is devoid of metals. The second dimer lacks Cu but has similar to20% occupancy of the Zn site and remains structurally similar to wild-type SOD1. The apo protein forms a continuous, extended arrangement of beta-barrels stacked up along the short crystallographic b-axis, while perpendicular to this axis, the constituent beta-strands form a zig-zag array of filaments, the overall arrangement of which has a similarity to the common structure associated with amyloid-like fibrils. (C) 2003 Elsevier Science Ltd. All rights reserved.
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