Download MendeleyStructures of Human Peroxiredoxin 3 Suggest Self-Chaperoning Assembly that Maintains Catalytic State.
Yewdall, N.A., Venugopal, H., Desfosses, A., Abrishami, V., Yosaatmadja, Y., Hampton, M.B., Gerrard, J.A., Goldstone, D.C., Mitra, A.K., Radjainia, M.(2016) Structure 24: 1120-1129
- PubMed: 27238969
- DOI: https://doi.org/10.1016/j.str.2016.04.013
- Primary Citation of Related Structures:
5JCG - PubMed 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.
Organizational 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.
