5 Citations (Scopus)


ERp57, a member of the protein disulfide isomerase family, is a ubiquitous disulfide cat-alyst that functions in the oxidative folding of various clients in the mammalian endoplasmic retic-ulum (ER). In concert with ER lectin-like chaperones calnexin and calreticulin (CNX/CRT), ERp57 functions in virtually all folding stages from co-translation to post-translation, and thus plays a critical role in maintaining protein homeostasis, with direct implication for pathology. Here, we present mechanisms by which Ca2+ regulates the formation of the ERp57-calnexin complex. Biochemical and isothermal titration calorimetry analyses revealed that ERp57 strongly interacts with CNX via a non-covalent bond in the absence of Ca2+. The ERp57-CNX complex not only promoted the oxidative folding of human leukocyte antigen heavy chains, but also inhibited client aggregation. These results suggest that this complex performs both enzymatic and chaperoning functions under abnormal physiological conditions, such as Ca2+ depletion, to effectively guide proper oxidative protein folding. The findings shed light on the molecular mechanisms underpinning crosstalk between the chaperone network and Ca2+.

Original languageEnglish
Article number2853
Issue number10
Publication statusPublished - 2021


  • Ca
  • Calnexin
  • Chaperone
  • Endoplasmic reticulum
  • ERp57
  • Human leukocyte antigen
  • Oxidative folding


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