| Chikashi Toyoshima | |
| Birth Date: | July 17, 1954 |
| Birth Place: | Akita, Japan |
| Citizenship: | Japan |
| Field: | Biophysics |
| Alma Mater: | University of Tokyo |
| Known For: | Calcium ATPase |
| Prizes: | Gregori Aminoff Prize (2016) |
is a Japanese biophysicist.[1] He is a professor at the University of Tokyo and the Foreign Associate of the National Academy of Sciences, USA.[2] His research focuses on two proteins: the Ca2+-ATPase, and the Na+, K+-ATPase.[3] Toyoshima's research about the Ca2+-ATPase started in 1989. He and his colleagues obtained the world's first series of images of Ca2+-ATPase at the atomic level.[4] Via x-ray crystallography, cryo-EM and other methods, he has determined the crystal structures of ten intermediates of Ca2+-ATPase. On September 10, 2015, The Royal Swedish Academy of Sciences awarded him and Poul Nissen the Gregori Aminoff Prize of 2016 for their fundamental contributions to understanding the structural basis for ATP-driven translocation of ions across membranes.[5]
Toyoshima was born in Honjo in the prefecture of Akita, Japan. Toyoshima and his older brother worked on science experiments with their mother, a high school home economics teacher,[6] and were successful in science research contests throughout Akita. In 1973, he was admitted by the University of Tokyo on his first trial. In his first two years, he studied standard physics while also taking classes in the biochemistry and botany departments. In the middle of his third year, he visited Setsuro Ebashi's laboratory, which worked with electron microscopes. He continued to research the microscopy of thin muscle filaments and myosin heads for his master's and doctoral research in Ebashi's laboratory after he received his undergraduate degree in 1978. He completed his PhD in 1983.[1] [4]
In 1984, Toyoshima became a research associate at the University of Tokyo. Two years later, he took a postdoctoral position at the laboratory of biophysicist Nigel Unwin at Stanford University. Under Unwin, Toyoshima worked to develop mathematical methods for disentangling the superimposed information from a projection image, or electron micrograph, of a tubular structure. In 1988, he followed Unwin to the Medical Research Council's Laboratory of Molecular Biology, where he met fellow biophysicist David Stokes, who was studying Ca2+-ATPase. He also worked with Stokes. After moving back to Japan in 1989, he joined the Frontier Research Program at RIKEN as a research scientist. He moved to the Tokyo Institute of Technology as an associate professor in 1990. In 1994, Toyoshima was offered a faculty position at the University of Tokyo, where he is currently a professor at the Center for Structural Biology of Challenging Proteins within the Institute of Molecular and Cellular Biosciences.[1] [3] [4]
Early in his research career, Toyoshima worked on "3D image analysis of muscle thin filaments decorated by myosin heads" as an electron microscopist in the Department of Physics at the University of Tokyo.[7] He later conducted acetylcholine receptor research after he went to Unwin's laboratory to study cryogenic electron microscopy (cryo-EM) in 1986. By developing a new mathematical algorithm to untangle the superimposed images obtained from the cryo-EM, he managed to reconstruct the 3D structure of an ion channel at 17 Å resolution.[8] This was the first 3D structure of the ion channel.[3] Soon afterward, the same method was applied to reconstruct the 3D structure of Ca2+-ATPase with help from David Stokes. Toyoshima and Stokes published their analysis of the structure of this protein in Nature in 1993.[9] After returning to Japan, Toyoshima's later research continued to focus on the structure of Ca2+-ATPase. Through combining the x-ray crystallography and the crystallization methods for electron microscopy, Toyoshima obtained and photographed large crystals of Ca2+-ATPase in their first state, the E1·2Ca2+. He published his research—the first high-resolution images of P-type ATPases—in 2000.[10] Over the following years, he published a series of crystal structures of Ca2+-ATPase. As of 2023, he has determined the crystal structures of this ATPase in ten different states by x-ray crystallography, covering roughly the entire reaction cycle. He also extended his research to Na+, K+-ATPase[11] and has developed a methodology for electron crystallography of ultrathin 3D protein crystals.[12]