Cryo-electron microscopy structure of human peroxiredoxin-3 filament reveals the assembly of a putative chaperone.
Peroxiredoxins (Prxs) are a ubiquitous class of thiol-dependent peroxidases that play an important role in the protection and response of cells to oxidative stress. The catalytic unit of typical 2-Cys Prxs are homodimers, which can self-associate to form complex assemblies that are hypothesized to have signaling and chaperone activity. Mitochondrial Prx3 forms dodecameric toroids, which can further stack to form filaments, the so-called high-molecular-weight (HMW) form that has putative holdase activity. We used single-particle analysis and helical processing of electron cryomicroscopy images of human Prx3 filaments induced by low pH to generate a ∼7-Å resolution 3D structure of the HMW form, the first such structure for a 2-Cys Prx. The pseudo-atomic model reveals interactions that promote the stacking of the toroids and shows that unlike previously reported data, the structure can accommodate a partially folded C terminus. The HMW filament lumen displays hydrophobic patches, which we hypothesize bestow holdase activity.
School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand.
Mazdak
M
Radjainia
School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand.
Hariprasad
H
Venugopal
School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand.
Ambroise
A
Desfosses
Izon Science Limited, 8c Homersham Place, Burnside, Christchurch 8053, New Zealand; Biomolecular Interaction Centre and School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand; MacDiarmid Institute for Advanced Materials and Nanotechnology, Victoria University, Wellington 6140, New Zealand.
Amy J
AJ
Phillips
Biomolecular Interaction Centre and School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand; MacDiarmid Institute for Advanced Materials and Nanotechnology, Victoria University, Wellington 6140, New Zealand.
N Amy
NA
Yewdall
Centre for Free Radical Research, Department of Pathology, University of Otago Christchurch, Christchurch 8011, New Zealand.
Mark B
MB
Hampton
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; MacDiarmid Institute for Advanced Materials and Nanotechnology, Victoria University, Wellington 6140, New Zealand; School of Chemical Sciences, University of Auckland, 23 Symonds Street, Auckland 1010, New Zealand; Callaghan Innovation Research Limited, Lower Hutt 5040, New Zealand.
Juliet A
JA
Gerrard
School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand. Electronic address: a.mitra@auckland.ac.nz.
Alok K
AK
Mitra
D020134:Catalytic Domain; D020285:Cryoelectron Microscopy; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D061105:Peroxiredoxin III / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
D018832:Molecular Chaperones; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III