title: Structures of Human Peroxiredoxin 3 Suggest Self-Chaperoning Assembly that Maintains Catalytic State.
abstract: Peroxiredoxins are antioxidant proteins primarily responsible for detoxification of hydroperoxides in cells. On exposure to various cellular stresses, peroxiredoxins can acquire chaperone activity, manifested as quaternary reorganization into a high molecular weight (HMW) form. Acidification, for example, causes dodecameric rings of human peroxiredoxin 3 (HsPrx3) to stack into long helical filaments. In this work, a 4.1-Å resolution structure of low-pH-instigated helical filaments was elucidated, showing a locally unfolded active site and partially folded C terminus. A 2.8-Å crystal structure of HsPrx3 was determined at pH 8.5 under reducing conditions, wherein dodecameric rings are arranged as a short stack, with symmetry similar to low-pH filaments. In contrast to previous observations, the crystal structure displays both a fully folded active site and ordered C terminus, suggesting that the HsPrx3 HMW form maintains catalytic activity. We propose a new role for the HMW form as a self-chaperoning assembly maintaining HsPrx3 function under stress.
authors.affiliation: School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand; Biomolecular Interaction Centre and School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand.
authors.forename: N Amy
authors.initials: NA
authors.lastname: Yewdall
authors.affiliation: School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand.
authors.forename: Hariprasad
authors.initials: H
authors.lastname: Venugopal
authors.affiliation: School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand.
authors.forename: Ambroise
authors.initials: A
authors.lastname: Desfosses
authors.affiliation: Biocomputing Unit, Centro Nacional de Biotecnologia - CSIC, C/Darwin 3, 28049 Madrid, Spain.
authors.forename: Vahid
authors.initials: V
authors.lastname: Abrishami
authors.affiliation: School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand.
authors.forename: Yuliana
authors.initials: Y
authors.lastname: Yosaatmadja
authors.affiliation: Centre for Free Radical Research, Department of Pathology, University of Otago Christchurch, Christchurch 8011, New Zealand.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Hampton
authors.affiliation: School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand; MacDiarmid Institute for Advanced Materials and Nanotechnology, Victoria University, Wellington 6140, New Zealand; School of Chemical Sciences, University of Auckland, Auckland 1010, New Zealand; Callaghan Innovation Research Limited, Lower Hutt 5040, New Zealand.
authors.forename: Juliet A
authors.initials: JA
authors.lastname: Gerrard
authors.affiliation: School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand. Electronic address: d.goldstone@auckland.ac.nz.
authors.forename: David C
authors.initials: DC
authors.lastname: Goldstone
authors.affiliation: School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand. Electronic address: a.mitra@auckland.ac.nz.
authors.forename: Alok K
authors.initials: AK
authors.lastname: Mitra
authors.affiliation: School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand. Electronic address: mazdak.radjainia@monash.edu.
authors.forename: Mazdak
authors.initials: M
authors.lastname: Radjainia
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D061105:Peroxiredoxin III / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding
chemical_list: D061105:Peroxiredoxin III
keywords: X-Ray crystal structure; cryo-electron microscopy; high molecular weight form; molecular chaperone; peroxiredoxin