Cyclophilin 40: An Hsp90-cochaperone associated with apo-steroid receptors |
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| Authors: | Thomas Ratajczak Bryan K Ward Carmel Cluning Rudi K Allan |
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| Institution: | 1. Centre for Medical Research, The University of Western Australia, Nedlands, WA 6009, Australia;2. The Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA 6009, Australia;1. Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong;2. State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong;1. Department of Marine Life Sciences, Jeju National University, Jeju Self-Governing Province 63243, Republic of Korea;2. Fish Vaccine Research Center, Jeju National University, Jeju Self-Governing Province 63243, Republic of Korea;3. Department of Signal Transduction Sciences, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793;5. Department of Dermatology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793;6. Department of Cell Physiology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793;4. Nano-micro Structure Device Integrated Research Center, Kagawa University, 2217-20 Hayashi-cho, Takamatsu 761-0396, Japan;1. College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China;2. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210029, China;3. School of Life Science, Yunnan University, Kunming 650091, China;4. Traditional Chinese and Tibetan Medicine Research Centre, Medical College of Qinghai Univercity, Xining, 810001, China |
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| Abstract: | Cyclophilin 40, a divergent loop cyclophilin first identified in association with the estrogen receptor α, contains a C-terminal tetratricopeptide repeat domain through which it shares structural identity with FK506-binding protein 52 (FKBP52) and other partner cochaperones in steroid receptor-heat shock protein 90 (Hsp90) complexes. By dynamically competing for Hsp90 interaction, the cochaperones allow the receptors to establish distinct Hsp90-chaperone complexes, with the potential to exert tissue-specific control over receptor activity. Cyclophilin 40 regulates Hsp90 ATPase activity during receptor-Hsp90 assembly. Functional deletion of the cyclophilin 40 yeast homologue, Cpr7, adversely affected estrogen receptor α and glucocorticoid receptor activity that could be fully restored, either with wild type Cpr7 or Cpr7 with a cyclophilin domain lacking isomerase activity. We draw parallels with the mechanism already established for FKBP52 and propose that the cyclophilin 40 divergent loop interfaces with a contact surface on the steroid receptor ligand-binding domain to achieve an optimal orientation for receptor activity. |
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