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Tetramerization Reinforces the Dimer Interface of MnSOD

Journal Article · · PLoS ONE
 [1];  [2];  [3];  [3];  [4];  [5];  [6]
  1. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry; DOE/OSTI
  2. 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
  3. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry
  4. Univ. of California, Los Angeles, CA (United States). Dept. of Energy-Inst. for Genomics and Proteomics
  5. Brookhaven National Lab. (BNL), Upton, NY (United States)
  6. 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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Cited By (5)

Superoxide Dismutases and Superoxide Reductases journal January 2014
Protein-Protein Interactions in Candida albicans journal August 2019
The structure of the Caenorhabditis elegans manganese superoxide dismutase MnSOD-3-azide complex: C. elegans MnSOD Azide Complex journal August 2015
Human Mn-superoxide dismutase inactivation by peroxynitrite: a paradigm of metal-catalyzed tyrosine nitration in vitro and in vivo journal January 2018
Redox manipulation of the manganese metal in human manganese superoxide dismutase for neutron diffraction journal September 2018

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