Improved catenated structures of bovine peroxiredoxin III F190L reveal details of ring-ring interactions and a novel conformational state

Cao, Z., McGow, D. P., Shepherd, C. and Lindsay, J. G. (2015) Improved catenated structures of bovine peroxiredoxin III F190L reveal details of ring-ring interactions and a novel conformational state. PLoS ONE, 10(4), e0123303. (doi: 10.1371/journal.pone.0123303) (PMID:25906064) (PMCID:PMC4407889)

[img]
Preview
Text
105354.pdf - Published Version
Available under License Creative Commons Attribution.

2MB

Abstract

Mitochondrial 2-cys peroxiredoxin III (PrxIII) is a key player in antioxidant defence reducing locally-generated H2O2 to H2O. A Phe to Leu (F190L) mutation in the C-terminal α-helix of PrxIII, mimicking that found in some bacteria and parasites, increases its resistance to hyperoxidation but has no obvious influence on peroxidase activity. Here we report on the oxidized and reduced crystal structures of bovine PrxIII F190L at 2.4 Å and 2.2 Å, respectively. Both structures exist as two-ring catenanes with their dodecameric rings inclined at 55o to each other, similar to that previously reported for PrxIII C168S. The new higher-resolution structures reveal details of the complex network of H-bonds stabilising the inter-toroid contacts. In addition, Arg123, the key conserved residue, that normally interacts with the catalytic cys (Cp, cys 47) is found in a distinct conformation extending away from the Cp while the characteristic Arg-Glu-Arg network, underpinning the active-site geometry also displays a distinctive arrangement, not observed previously. This novel active-site organisation may provide new insights into the dynamics of the large-scale conformational changes occurring between oxidized and reduced states.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McGow, Miss Donna and Cao, Dr Zhenbo and Lindsay, Professor John Gordon
Authors: Cao, Z., McGow, D. P., Shepherd, C., and Lindsay, J. G.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in PLoS ONE 10(4):e0123303
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
453591Structure-function analysis of a key mitochondrial PrxIII antioxidant defence pathway: roles in antioxidant defence and chaperone-mediated protectionJohn Gordon LindsayBiotechnology and Biological Sciences Research Council (BBSRC)BB/F001851/1RI MOLECULAR CELL & SYSTEMS BIOLOGY