Structures of Human Peroxiredoxin 3 Suggest Self-Chaperoning Assembly that Maintains Catalytic State

N.  Amy Yewdall, Hariprasad Venugopal, Ambroise Desfosses, Vahid Abrishami, Yuliana Yosaatmadja, Mark B B. Hampton, Juliet A A. Gerrard, David C C. Goldstone, Alok K Mitra, Mazdak Radjainia

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25 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1120-1129
Number of pages10
Issue number7
Publication statusPublished - 6 Jul 2016


  • cryo-electron microscopy
  • high molecular weight form
  • molecular chaperone
  • peroxiredoxin
  • X-Ray crystal structure

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