Tetramerization Reinforces the Dimer Interface of MnSOD
- Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry; DOE/OSTI
- Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry; Univ. of Arizona, Tucson, AZ (United States). Dept. of Chemical and Environmental Engineering
- Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry
- Univ. of California, Los Angeles, CA (United States). Dept. of Energy-Inst. for Genomics and Proteomics
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry; Ewha Womans Univ., Seoul (Korea). Dept. of Bioinspired Science
Two yeast manganese superoxide dismutases (MnSOD), one from Saccharomyces cerevisiae mitochondria (ScMnSOD) and the other from Candida albicans cytosol (CaMnSODc), have most biochemical and biophysical properties in common, yet ScMnSOD is a tetramer and CaMnSODc is a dimer or ‘‘loose tetramer’’ in solution. Although CaMnSODc was found to crystallize as a tetramer, there is no indication from the solution properties that the functionality of CaMnSODc in vivo depends upon the formation of the tetrameric structure. To elucidate further the functional significance of MnSOD quaternary structure, wild-type and mutant forms of ScMnSOD (K182R, A183P mutant) and CaMnSODc (K184R, L185P mutant) with the substitutions at dimer interfaces were analyzed with respect to their oligomeric states and resistance to pH, heat, and denaturant. Dimeric CaMnSODc was found to be significantly more subject to thermal or denaturant-induced unfolding than tetrameric ScMnSOD. The residue substitutions at dimer interfaces caused dimeric CaMnSODc but not tetrameric ScMnSOD to dissociate into monomers. We conclude that the tetrameric assembly strongly reinforces the dimer interface, which is critical for MnSOD activity.
- Research Organization:
- Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division
- Grant/Contract Number:
- AC02-98CH10886
- OSTI ID:
- 1627605
- Journal Information:
- PLoS ONE, Journal Name: PLoS ONE Journal Issue: 5 Vol. 8; ISSN 1932-6203
- Publisher:
- Public Library of ScienceCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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