IQB Handbook

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43ACHIEVEMENTPUBLICATIONNorimatsu Y, Hasegawa K, Shimizu N, Toyoshima C. Protein-phospholipid interplay revealed with crystals of a calcium pump. Nature. 2017 May 11;545(7653):193-198. DOI:10.1038/nature22357Toyoshima C, Nakasako M, Nomura H, Ogawa H. Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution. Nature. 2000 Jun 8;405(6787):647-55. DOI:10.1038/35015017Imperial Award / Japan Academy Prize　 ”Elucidation of the operational mechanism of ion pumps, based on their atomic structures” 2018 June(1) Various stages in understanding of the Ca2+-pump. As we have succeeded in determining the atomic structures for most of the reaction intermediates, we can now understand the mechanism based on the atomic structure. (2) Two of our works have been introduced as Nature’s cover images. (3) From our studies, we now understand that so many things from lipid bilayer to protons are integrated as parts of the mechanism of the Ca2+-pump. TOYOSHIMACHIKASHIPH.D. (1983) THE UNIVERSITY OF TOKYORESEARCH ASSOCIATE (1984) THE UNIVERSITY OF TOKYOSCIENTIFIC STAFF (1988) MEDICAL RESEARCH COUNCIL LABORATORY OF MOLECULAR BIOLOGYRESEARCH SCIENTIST (1989) RIKENASSOCIATE PROFESSOR (1990) TOKYO INSTITUTE OF TECHNOLOGYPROFESSOR (1994) INSTITUTE OF MOLECULAR AND CELLULAR BIOSCIENCES, THE UNIVERSITY OF TOKYOPROFESSOR (2018) IQB / INSTITUTE FOR QUANTITATIVE BIOSCIENCES, THE UNIVERSITY OF TOKYOPROJECT PROFESSOR (2020) IQB / INSTITUTE FOR QUANTITATIVE BIOSCIENCES, THE UNIVERSITY OF TOKYO●MEMBER■ PROJECT PROFESSOR :TOYOSHIMA CHIKASHI ■ ASSOCIATE PROFESSOR :OGAWA HARUO■ PROJECT RESEARCH ASSOCIATE : KABASHIMA YOSHIKI■ PROJECT RESEARCH ASSOCIATE : KANAI RYUTA■ PROJECT RESEARCHER : TSUNEKAWA NAOKI■ PROJECT RESEARCHER :KODAMA MASAMI■ PROJECT ACADEMIC SUPPORT STAFF :MOTOYAMA KANNA■ PROJECT ACADEMIC SUPPORT STAFF :NAKAJIMA RIE■ PROJECT ACADEMIC SUPPORT STAFF :IZUMIKAWA KEI■ PROJECT ACADEMIC SUPPORT STAFF :KURAKATA MARIKO■ PROJECT ACADEMIC SUPPORT STAFF :YAMAMOTO YOKOPUBLICATIONAWARDince proteins have to change their three-dimensional structures to achieve their functions, it is impossible to understand how they work without knowing their 3D structures. We aim at understanding the functions of important proteins based on the atomic structures using X-ray crystallography as the principal tool. We focus on the structural basis of active ion transport and have already succeeded in determining the atomic struc-tures for 10 different states that nearly cover the entire reaction cycle of the calcium pump (3). As a result, we now roughly understand how ion pumps work and can answer funda-mental questions, e.g. what ATP and phos-phorylation do. Crystal structures represent, however, only a few points in the reaction cycle and protons, which play important roles in structural changes and functions, are invisible to X-ray. Therefore, theoretical calculations are also important in our study. We have also established an expression system using mammalian cell culture and succeeded in crystal structure analysis of a mutant. Such technology is unique and will become more and more important. Another principal target of our study, in collaboration with a Danish group, is the sodium pump (2, 4), which is expressed in all animal cells and deeply implicated in many diseases. These results have been recognized world-wide and Prof. Toyoshima was elected to prestigious Foreign Associate of the National Academy of Science, U.S.A. and Honorary Skou Professor at Aarhus Univ.Denmark. His lectures and interview can be seen on YouTube. He was also awarded a Medal with Purple Ribbon in 2015, Gregori Aminoff Prize in 2016 and the Imperial and Japan Academy Prizes in 2018.S