TY - JOUR
T1 - Structures of mouse SOD1 and human/mouse SOD1 chimeras
AU - Seetharaman, Sai V.
AU - Taylor, Alexander B.
AU - Holloway, Stephen
AU - Hart, P. J.
N1 - Funding Information:
This work was supported by Grants from the NIH-NINDS R01-NS39112 (to PJH), P01-NS04913 (to JSV, DRB, and PJH). SVS was supported in part by the William and Ella Owens Medical Research Foundation and the Judith and Jean Pape Adams Charitable Foundation. Support for the X-ray Crystallography Core Laboratory by the UTHSCSA Executive Research Committee and the San Antonio Cancer Institute is also gratefully acknowledged. We thank Celeste Karch, Mercedes Prudencio, and David Borchelt for continued collaboration and invaluable insight into the biological aspects of aggregation of SOD1 and the SOD1 chimera structures described in this paper.
PY - 2010/11/15
Y1 - 2010/11/15
N2 - Mutations in human copper-zinc superoxide dismutase (SOD1) cause an inherited form of amyotrophic lateral sclerosis (ALS). Inclusions enriched in pathogenic SOD1 accumulate in the spinal cords of transgenic mice expressing these proteins, but endogenous mouse SOD1 is not found as a component of these aggregates. In the accompanying paper, Karch and colleagues analyze aggregation propensities of human/mouse SOD1 chimeras in cell culture and identify two sequence elements in the human enzyme that seem to enhance its aggregation relative to the mouse enzyme. Here, we report the first structure of mouse SOD1 along with those of SOD1 chimeras in which residues 1-80 come from human SOD1 and residues 81-153 come from mouse SOD1 and vice versa. Taken together, the structural and cell-based data suggest a model in which residues Q42 and Q123 in mouse SOD1 modulate non-native SOD1-SOD1 intermolecular interactions at edge strands in the SOD1 Greek key β-barrel.
AB - Mutations in human copper-zinc superoxide dismutase (SOD1) cause an inherited form of amyotrophic lateral sclerosis (ALS). Inclusions enriched in pathogenic SOD1 accumulate in the spinal cords of transgenic mice expressing these proteins, but endogenous mouse SOD1 is not found as a component of these aggregates. In the accompanying paper, Karch and colleagues analyze aggregation propensities of human/mouse SOD1 chimeras in cell culture and identify two sequence elements in the human enzyme that seem to enhance its aggregation relative to the mouse enzyme. Here, we report the first structure of mouse SOD1 along with those of SOD1 chimeras in which residues 1-80 come from human SOD1 and residues 81-153 come from mouse SOD1 and vice versa. Taken together, the structural and cell-based data suggest a model in which residues Q42 and Q123 in mouse SOD1 modulate non-native SOD1-SOD1 intermolecular interactions at edge strands in the SOD1 Greek key β-barrel.
KW - Amyotrophic lateral sclerosis
KW - Copper-zinc superoxide dismutase
KW - Protein aggregation
KW - X-ray crystallography
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U2 - 10.1016/j.abb.2010.08.014
DO - 10.1016/j.abb.2010.08.014
M3 - Article
C2 - 20727846
AN - SCOPUS:77957021567
SN - 0003-9861
VL - 503
SP - 183
EP - 190
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -