Ca<sup>2+</sup> Regulates ERp57-Calnexin Complex Formation
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 virt...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/10/2853 |
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| author | Yuya Tanikawa Shingo Kanemura Dai Ito Yuxi Lin Motonori Matsusaki Kimiko Kuroki Hiroshi Yamaguchi Katsumi Maenaka Young-Ho Lee Kenji Inaba Masaki Okumura |
| author_facet | Yuya Tanikawa Shingo Kanemura Dai Ito Yuxi Lin Motonori Matsusaki Kimiko Kuroki Hiroshi Yamaguchi Katsumi Maenaka Young-Ho Lee Kenji Inaba Masaki Okumura |
| author_sort | Yuya Tanikawa |
| collection | DOAJ |
| description | 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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup>. 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 Ca<sup>2+</sup> depletion, to effectively guide proper oxidative protein folding. The findings shed light on the molecular mechanisms underpinning crosstalk between the chaperone network and Ca<sup>2+</sup>. |
| first_indexed | 2024-03-10T11:32:01Z |
| format | Article |
| id | doaj.art-b328a3b2ab504ed68bb56b8aa12976b2 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T11:32:01Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b328a3b2ab504ed68bb56b8aa12976b22023-11-21T19:11:44ZengMDPI AGMolecules1420-30492021-05-012610285310.3390/molecules26102853Ca<sup>2+</sup> Regulates ERp57-Calnexin Complex FormationYuya Tanikawa0Shingo Kanemura1Dai Ito2Yuxi Lin3Motonori Matsusaki4Kimiko Kuroki5Hiroshi Yamaguchi6Katsumi Maenaka7Young-Ho Lee8Kenji Inaba9Masaki Okumura10School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, JapanSchool of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, JapanDepartment of Brain and Cognitive Science, Daegu Gyeongbuk Institute of Science and Technology, 333 Techno Jungang Daero, Daegu 42988, KoreaResearch Center for Bioconvergence Analysis, Korea Basic Science Institute, 162 Yeongudanji-ro, Ochang, Cheongju 28119, KoreaFrontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramakiaza Aoba, Aoba-ku, Sendai 980-8578, JapanLaboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Nishi 6, Kita 12, Kita-ku, Sapporo 060-0812, JapanSchool of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, JapanLaboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Nishi 6, Kita 12, Kita-ku, Sapporo 060-0812, JapanResearch Center for Bioconvergence Analysis, Korea Basic Science Institute, 162 Yeongudanji-ro, Ochang, Cheongju 28119, KoreaInstitute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, JapanFrontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramakiaza Aoba, Aoba-ku, Sendai 980-8578, JapanERp57, 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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup>. 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 Ca<sup>2+</sup> depletion, to effectively guide proper oxidative protein folding. The findings shed light on the molecular mechanisms underpinning crosstalk between the chaperone network and Ca<sup>2+</sup>.https://www.mdpi.com/1420-3049/26/10/2853endoplasmic reticulumoxidative foldingchaperonecalnexinERp57human leukocyte antigen |
| spellingShingle | Yuya Tanikawa Shingo Kanemura Dai Ito Yuxi Lin Motonori Matsusaki Kimiko Kuroki Hiroshi Yamaguchi Katsumi Maenaka Young-Ho Lee Kenji Inaba Masaki Okumura Ca<sup>2+</sup> Regulates ERp57-Calnexin Complex Formation Molecules endoplasmic reticulum oxidative folding chaperone calnexin ERp57 human leukocyte antigen |
| title | Ca<sup>2+</sup> Regulates ERp57-Calnexin Complex Formation |
| title_full | Ca<sup>2+</sup> Regulates ERp57-Calnexin Complex Formation |
| title_fullStr | Ca<sup>2+</sup> Regulates ERp57-Calnexin Complex Formation |
| title_full_unstemmed | Ca<sup>2+</sup> Regulates ERp57-Calnexin Complex Formation |
| title_short | Ca<sup>2+</sup> Regulates ERp57-Calnexin Complex Formation |
| title_sort | ca sup 2 sup regulates erp57 calnexin complex formation |
| topic | endoplasmic reticulum oxidative folding chaperone calnexin ERp57 human leukocyte antigen |
| url | https://www.mdpi.com/1420-3049/26/10/2853 |
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