首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Structure of the Human TELO2-TTI1-TTI2 Complex
Institution:1. Department of Life Science, Pohang University of Science and Technology, Pohang 37673, South Korea;2. Center for Genomic Integrity Institute for Basic Science (IBS), UNIST, Ulsan 44919, South Korea;3. Department of Biological Sciences & Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08832, South Korea;1. Department of Chemistry, University of Waterloo, Waterloo N2L 3G1, Ontario, Canada;2. Bristol Myers Squibb, Cambridge, MA 02140, United States;1. Biophysics Program, The University of Michigan, Ann Arbor, MI 48109, USA;2. Department of Chemistry, Biomedical Engineering, and Macromolecular Science and Engineering, The University of Michigan, Ann Arbor, MI 48109, USA;3. College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA;4. Bio-AFM Frontier Research Center, Kanazawa University, Kanazawa 9201192, Japan;5. Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA;6. Department of Chemistry, Technische Universität München, Garching 85748, Germany;1. Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455 USA;2. Division of Basic Sciences, School of Dentistry, University of Minnesota - Twin Cities, Minneapolis, MN 55455 USA;3. Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455 USA;4. Dept. of Microbiology & Immunology, University of Minnesota - Twin Cities, Minneapolis, MN 55455 USA;1. Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan;2. Department of Bioscience, Faculty of Science, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan;3. Course of Biological Science, Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan;1. School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, 3216 Geelong, Australia;2. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, 3168 Melbourne, Australia;3. Department of Biochemistry and Pharmacology and The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, 3052 Melbourne, Australia;4. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia;5. Ophthalmology, University of Melbourne, Department of Surgery Melbourne, Victoria 3000, Australia;6. Department of Molecular and Translational Science, Monash University, 3168 Melbourne, Australia;1. Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA;2. Saha Cardiovascular Research Center, College of Medicine, University of Kentucky, Lexington, KY 40536, USA
Abstract:Phosphatidylinositol 3-kinase-related protein kinases (PIKKs) play critical roles in various metabolic pathways related to cell proliferation and survival. The TELO2-TTI1-TTI2 (TTT) complex has been proposed to recognize newly synthesized PIKKs and to deliver them to the R2TP complex (RUVBL1-RUVBL2-RPAP3-PIH1D1) and the heat shock protein 90 chaperone, thereby supporting their folding and assembly. Here, we determined the cryo-EM structure of the TTT complex at an average resolution of 4.2 Å. We describe the full-length structures of TTI1 and TELO2, and a partial structure of TTI2. All three proteins form elongated helical repeat structures. TTI1 provides a platform on which TELO2 and TTI2 bind to its central region and C-terminal end, respectively. The TELO2 C-terminal domain (CTD) is required for the interaction with TTI1 and recruitment of Ataxia-telangiectasia mutated (ATM). The N- and C-terminal segments of TTI1 recognize the FRAP-ATM-TRRAP (FAT) domain and the N-terminal HEAT repeats of ATM, respectively. The TELO2 CTD and TTI1 N- and C-terminal segments are required for cell survival in response to ionizing radiation.
Keywords:PIKKs  TELO2-TTI1-TTI2 complex  protein folding  protein stability  cryo-EM  ATM"}  {"#name":"keyword"  "$":{"id":"k0035"}  "$$":[{"#name":"text"  "_":"ataxia-telangiectasia mutated  cryo-EM"}  {"#name":"keyword"  "$":{"id":"k0045"}  "$$":[{"#name":"text"  "_":"cryo-electron microscopy  FAT"}  {"#name":"keyword"  "$":{"id":"k0055"}  "$$":[{"#name":"text"  "_":"FRAP-ATM-TRRAP  HEAT"}  {"#name":"keyword"  "$":{"id":"k0065"}  "$$":[{"#name":"text"  "_":"Huntingtin  elongation factor 3  protein phosphatase 2A  and yeast kinase TOR1  HSP90"}  {"#name":"keyword"  "$":{"id":"k0075"}  "$$":[{"#name":"text"  "_":"heat shock protein 90  PIKKs"}  {"#name":"keyword"  "$":{"id":"k0085"}  "$$":[{"#name":"text"  "_":"phosphatidylinositol 3-kinase-related protein kinases  R2TP"}  {"#name":"keyword"  "$":{"id":"k0095"}  "$$":[{"#name":"text"  "_":"RUVBL1-RUVBL2-RPAP3-PIH1D1  TTT"}  {"#name":"keyword"  "$":{"id":"k0105"}  "$$":[{"#name":"text"  "_":"TELO2-TTI1-TTI2  XL-MS"}  {"#name":"keyword"  "$":{"id":"k0115"}  "$$":[{"#name":"text"  "_":"crosslinking mass spectrometry
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号