Functional Interplay between P5 and PDI/ERp72 to Drive Protein Folding
1
Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3, Aramakiaza Aoba, Aoba-ku, Sendai 980-8578, Japan
2
Institute of Advanced Medical Sciences, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan
3
School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda 669-1337, Japan
4
Department of Brain and Cognitive Science, Daegu Gyeongbuk Institute of Science and Technology, 333, Techno Jungang Daero, Daegu 42988, Korea
5
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, 162, Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si 28119, Korea
6
Bio-Analytical Science, University of Science and Technology, 217, Gajeong-ro, Yuseong-gu, Daejeon 34113, Korea
7
Graduate School of Analytical Science and Technology, Chungnam National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Korea
8
Research Headquarters, Korea Brain Research Institute, 61, Cheomdan-ro, Dong-gu, Daegu 41068, Korea
9
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editor: Clive R. Bramham
Biology 2021, 10(11), 1112; https://doi.org/10.3390/biology10111112
Received: 29 September 2021
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Revised: 21 October 2021
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Accepted: 27 October 2021
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Published: 28 October 2021
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
Simple Summary
The physiological functions of proteins are destined by their unique three-dimensional structures. Almost all biological kingdoms share conserved disulfide-catalysts and chaperone networks that assist in correct protein folding and prevent aggregation. Disruption of these networks is implicated in pathogenesis, including neurodegenerative disease. In the mammalian endoplasmic reticulum (ER), more than 20 members of the protein disulfide isomerase family (PDIs) are believed to cooperate in the client folding pathway, but it remains unclear whether complex formation among PDIs via non-covalent interaction is involved in regulating their enzymatic and chaperone functions. Herein, we report novel functional hetero complexes between PDIs that promote oxidative folding and inhibit aggregation along client folding. The findings provide insight into the physiological significance of disulfide-catalyst and chaperone networks and clues for understanding pathogenesis associated with disruption of the networks.
P5 is one of protein disulfide isomerase family proteins (PDIs) involved in endoplasmic reticulum (ER) protein quality control that assists oxidative folding, inhibits protein aggregation, and regulates the unfolded protein response. P5 reportedly interacts with other PDIs via intermolecular disulfide bonds in cultured cells, but it remains unclear whether complex formation between P5 and other PDIs is involved in regulating enzymatic and chaperone functions. Herein, we established the far-western blot method to detect non-covalent interactions between P5 and other PDIs and found that PDI and ERp72 are partner proteins of P5. The enzymatic activity of P5-mediated oxidative folding is up-regulated by PDI, while the chaperone activity of P5 is stimulated by ERp72. These findings shed light on the mechanism by which the complex formations among PDIs drive to synergistically accelerate protein folding and prevents aggregation. This knowledge has implications for understanding misfolding-related pathology.
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Keywords:
protein disulfide isomerase family; disulfide bond; endoplasmic reticulum; oxidative folding; molecular chaperone; protein-protein interaction
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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MDPI and ACS Style
Matsusaki, M.; Okada, R.; Tanikawa, Y.; Kanemura, S.; Ito, D.; Lin, Y.; Watabe, M.; Yamaguchi, H.; Saio, T.; Lee, Y.-H.; Inaba, K.; Okumura, M. Functional Interplay between P5 and PDI/ERp72 to Drive Protein Folding. Biology 2021, 10, 1112. https://doi.org/10.3390/biology10111112
AMA Style
Matsusaki M, Okada R, Tanikawa Y, Kanemura S, Ito D, Lin Y, Watabe M, Yamaguchi H, Saio T, Lee Y-H, Inaba K, Okumura M. Functional Interplay between P5 and PDI/ERp72 to Drive Protein Folding. Biology. 2021; 10(11):1112. https://doi.org/10.3390/biology10111112
Chicago/Turabian StyleMatsusaki, Motonori, Rina Okada, Yuya Tanikawa, Shingo Kanemura, Dai Ito, Yuxi Lin, Mai Watabe, Hiroshi Yamaguchi, Tomohide Saio, Young-Ho Lee, Kenji Inaba, and Masaki Okumura. 2021. "Functional Interplay between P5 and PDI/ERp72 to Drive Protein Folding" Biology 10, no. 11: 1112. https://doi.org/10.3390/biology10111112
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