Tetramerization reinforces the dimer interface of MnSOD.

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&qu...

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Main Authors: Yuewei Sheng, Armando Durazo, Mikhail Schumacher, Edith Butler Gralla, Duilio Cascio, Diane E Cabelli, Joan Selverstone Valentine
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3646814?pdf=render
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author Yuewei Sheng
Armando Durazo
Mikhail Schumacher
Edith Butler Gralla
Duilio Cascio
Diane E Cabelli
Joan Selverstone Valentine
author_facet Yuewei Sheng
Armando Durazo
Mikhail Schumacher
Edith Butler Gralla
Duilio Cascio
Diane E Cabelli
Joan Selverstone Valentine
author_sort Yuewei Sheng
collection DOAJ
description 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.
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spelling doaj.art-b280228096144303a207cfcc58a82c942022-12-22T00:59:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6244610.1371/journal.pone.0062446Tetramerization reinforces the dimer interface of MnSOD.Yuewei ShengArmando DurazoMikhail SchumacherEdith Butler GrallaDuilio CascioDiane E CabelliJoan Selverstone ValentineTwo 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.http://europepmc.org/articles/PMC3646814?pdf=render
spellingShingle Yuewei Sheng
Armando Durazo
Mikhail Schumacher
Edith Butler Gralla
Duilio Cascio
Diane E Cabelli
Joan Selverstone Valentine
Tetramerization reinforces the dimer interface of MnSOD.
PLoS ONE
title Tetramerization reinforces the dimer interface of MnSOD.
title_full Tetramerization reinforces the dimer interface of MnSOD.
title_fullStr Tetramerization reinforces the dimer interface of MnSOD.
title_full_unstemmed Tetramerization reinforces the dimer interface of MnSOD.
title_short Tetramerization reinforces the dimer interface of MnSOD.
title_sort tetramerization reinforces the dimer interface of mnsod
url http://europepmc.org/articles/PMC3646814?pdf=render
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AT duiliocascio tetramerizationreinforcesthedimerinterfaceofmnsod
AT dianeecabelli tetramerizationreinforcesthedimerinterfaceofmnsod
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