The Royal Swedish Academy of Sciences has decided to award the Gregori Aminoff Prize in crystallography 2016 to Professor Poul Nissen, Aarhus University, Denmark, and Professor Chikashi Toyoshima, University of Tokyo, Japan, “for their fundamental contributions to understanding the structural basis for ATP-driven translocation of ions across membranes”. The prize amount to in total 100.000SEK.
Scientists awarded for understanding of transport of ions through cell membranes
Crystallography is a key technology to determine molecular structures in physics, chemistry and biology. These structures enable us to understand the characteristics of materials and chemicals, but also the function of biological macromolecules as proteins and DNA.
Pär Nordlund, Chair of the Aminoff Prize Committee, says:
– The Laureates has developed a new technology to crystallise and determine structures of membrane proteins in their natural environment. The major breakthrough is that the study has enabled us to understand the mechanism of transport of ions through cell membranes, to understand intermediate states in this very complex system.
To use structured information of this kind nowadays plays a very important role in the process of making new pharmaceutical drugs.
Professors Chikashi Toyoshima and Poul Nissen have determined crystal structures of several key members of the P-type ATPase family and established structures of essential intermediates in their ion transport cycles, information which has lead to the detailed description of molecular mechanisms of these important ion translocation systems.
The P-type ATPases constitutes a major family of membrane ion pumps found in all kingdoms of life. They catalyse the chemical driven translocation of a range of different cations over biological membranes including Ca2+,K+, Na+ and H+ as well as several transition and post transition metals. The ion concentration gradients generated by P-type ATPases across biological membranes provide driving forces for many other biological processes, but also play prominent roles in cell signaling and regulation.
P-type ATPases are large multi-domain integral membrane proteins that undergo distinct conformational changes along the ion transport cycle and are therefor particularly challenging for crystallographic work. Toyoshima solved the first crystal structure of a P-type ATPase in 2000, the structure of the Ca+2-ATPase SERCA. To accomplish this he developed novel crystallization techniques allowing three-dimensional protein crystal to be grown within a phospholipid environment. He subsequently determined the SERCA Ca+2-ATPase structure in several trapped conformational states of the transport cycle. This work provided the fundament for the initial description of the structural basis for ion transport by a P-type ATPase. Nissen has also studied trapped conformational states of SERCA but in addition determined structures of P-type ATPases of other subfamilies including the Na+/K+, H+, and most recently copper and zinc P1B-type ATPases. His work also include the developed of novel strategies for trapping and crystallizing intermediates in the ion transport cycle of P-type ATPases. The independent and largely complementary work of these two scientist have lead to fascinating insights into to these molecular machines; the structural basis for the dramatic structural changes seen between different intermediates of the ion transport cycle; the sophisticated fine tuning of ion binding and release; the establishment of selectivity for specific ions; the dynamic formation of ion excite and entrance channels; and the molecular basis for how chemical energy from ATP is utilized to drive the structural transformations.
Paul Nissen, born 1967 obtained his PhD at Aarhus University, Denmark, in 1997 followed by a postdoctoral period at Yale University. In 2000 he returned to Aarhus University where he is now Professor of Protein Biochemistry, as well as Director of the Danish Research Institute of Translational Neuroscience and the PUMPkin Centre.
Chikashi Toyoshima, born 1954, obtained his DSc degree in 1983 from University of Tokyo, Japan. After a postdoctoral period at Stanford University, USA and University of Cambridge, UK, he returned in 1989 to Japan and is now Professor of Protein Biochemistry and Director of the Center for Bioinformatics at University of Tokyo.
The Lauretaes personal accounts of their research achievements in Physica Scripta
Poul Nissens article will soon be available.
Chikashi Toyoshima – The road to understanding an ion pump