Ca2+ Regulates ERp57-Calnexin Complex Formation

Molecules

Dai Ito¹  Motonori Matsusaki²  Masaki Okumura²  Kenji Inaba³  Kimiko Kuroki⁴  Katsumi Maenaka⁴  Yuxi Lin⁵  Young-Ho Lee⁵  Yuya Tanikawa⁶  Shingo Kanemura⁶  Hiroshi Yamaguchi⁶ 

[1] Department of Brain and Cognitive Science, Daegu Gyeongbuk Institute of Science and Technology, 333 Techno Jungang Daero, Daegu 42988, Korea;Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramakiaza Aoba, Aoba-ku, Sendai 980-8578, Japan;Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan;Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Nishi 6, Kita 12, Kita-ku, Sapporo 060-0812, Japan;Research Center for Bioconvergence Analysis, Korea Basic Science Institute, 162 Yeongudanji-ro, Ochang, Cheongju 28119, Korea;School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan;

关键词: endoplasmic reticulum;    oxidative folding;    chaperone;    calnexin;    ERp57;    human leukocyte antigen;   

DOI  :  10.3390/molecules26102853

来源: DOAJ

【 摘 要 】

ERp57, a member of the protein disulfide isomerase family, is a ubiquitous disulfide catalyst that functions in the oxidative folding of various clients in the mammalian endoplasmic reticulum (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⁺.

【 授权许可】

Unknown