"Structural biology of P-type ion translocating ATPases: towards complete understanding of the mechanism" Prof. Chikashi Toyoshima

Prof. Chikashi Toyoshima

Professor

Institute of Molecular and Cellular Biosciences

The University of Tokyo

Abstract

As proteins achieve their functions by changing conformation, determining their structures, preferably at an atomic resolution, must be a start point for true understanding of the mechanism. If the protein of interest undergoes several distinct intermediates in the reaction cycle, atomic structures need to be determined for all of them. My research interest is in P-type ion translocating ATPases, in particular, the Ca²⁺-pump or SERCA (sarco(endo)plasmic reticulum Ca²⁺-ATPase). SERCA is an almost ideally interesting protein to study. It is an ATP-driven ion pump that can establish a 10,000 fold difference in Ca²⁺ concentration across the membrane, with almost 100% energy efficiency. This pump rigorously selects Ca²⁺ in a milieu of, for instance, 100,000 times more concentrated Na⁺, which has a very similar ionic radius (0.95 vs. 0.99 Å). It is well known that Ca²⁺ is the ion most widely used for regulation of cellular processes. But why Ca²⁺, not Mg²⁺, for instance? SERCA also transports H⁺ in the opposite direction to Ca²⁺. However, as the sarcoplasmic reticulum (SR) membrane is leaky to H⁺, pumped protons return to the lumen of SR. Why is, then, H⁺ countertransport necessary? There are many questions to address. My research group has so far determined crystal structures for 10 reaction intermediates that just about cover the entire reaction cycle. As a result, we can propose a detailed scenario for ion pumping. Yet, the structural changes are so large and complex that it is often difficult to see how one follows the other and what drives the changes. In this talk, I would like to discuss how we can approach the ultimate goal: to understand why the structure of a P-type ATPase has to be so. 

Biography

Chikashi Toyoshima is Professor at the Institute of Molecular and Cellular Biosciences, The University of Tokyo. He received his D. Sc. degree from the Physics Department at the University of Tokyo in 1983. He was a postdoctoral fellow at Stanford University and at the MRC Laboratory of Molecular Biology, Cambridge, UK, before he assumed a position as Associate Professor at the Tokyo Institute of Technology in 1990. In 1994 he accepted his current position at the University of Tokyo. In 2005 he was elected as Foreign Associate of the National Academy of Sciences of the USA, and in 2007 he was elected as National Lecturer of the Biophysical Society, USA, and awarded the Hitchcock Professorship at the University of California, Berkeley. He was given an Asahi Prize in 2010 and endowed with the Medal with Purple Ribbon from Japan in 2015. He is also a recipient of the Gregori Aminoff Prize in 2016 from the Royal Swedish Academy of Sciences.