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RESEARCH FRONT
Contents Vol 65(5)

Molecular Mechanisms of K+ Selectivity in Na/K Pump

Haibo Yu A D , Ian Ratheal B , Pablo Artigas B and Benoît Roux C
+ Author Affiliations
- Author Affiliations

A School of Chemistry, University of Wollongong, NSW 2522, Australia.

B Department of Cell Physiology and Molecular Biophysics, Texas Tech Health Sciences Center, Lubbock, TX, USA.

C Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.

D Corresponding author. Email: hyu@uow.edu.au




Haibo Yu joined the University of Wollongong as a Lecturer in the School of Chemistry in July 2010. He completed his undergraduate degree at the University of Science and Technology of China (USTC) and his Ph.D. at the Swiss Federal Institute of Technology (ETH) Zürich under the supervision of Professor Wilfred F. van Gunsteren. He then conducted post-doctoral research at the University of Wisconsin-Madison with Professor Qiang Cui and the University of Chicago with Professor Benoît Roux in the United States. In November 2011, he was awarded an Australian Research Council Future Fellowship. His research interests focus on the development and application of theoretical and computational models to understand the structure-dynamics-function relationship in complex biomolecular systems.


Ian Ratheal studied biology at the University of Texas Tech. He worked on Na/K ATPase research with Professor Pablo Artigas during his undergraduate education and continued after graduation as a research technician. Now he is enjoying medical school at the Texas Tech Health Science Center.


Pablo Artigas studied biology and biophysics at the University of the Republic, in Montevideo, Uruguay. He obtained a M.S. in 1999 (studying cardiac Ca channels with Professors G. Pizarro and G. Brum), and a Ph.D. in 2002 (his thesis focused on Na/K pump mechanism, with D. C. Gadsby as advisor). After his post-doctoral research at Rockefeller University, he joined the Texas Tech University Health Sciences Center in 2007 and has continued his investigations into the relationship between the Na/K pump structure and its mechanism, with particular emphasis on intramolecular interactions and the mechanisms of ion binding and ion selectivity.


Benoît Roux first studied physics and biophysics at the University of Montréal. In 1990, he obtained a Ph.D. in biophysics from Harvard University under the direction of Martin Karplus. In the last decade, he has held positions at the University of Montréal and the Weill Medical College of Cornell University. Since 2005, he has been Professor in the Department of Biochemistry and Molecular Biology at the University of Chicago, with a joint appointment as Senior Computational Biologist at Argonne National Laboratory.

Australian Journal of Chemistry 65(5) 448-456 https://doi.org/10.1071/CH12026
Submitted: 19 January 2012  Accepted: 19 February 2012   Published: 24 April 2012

Abstract

The sodium–potassium (Na/K) pump plays an essential role in maintaining cell volume and secondary active transport of other solutes by establishing the Na+ and K+ concentration gradients across the plasma membrane of animal cells. The recently determined crystal structures of the Na/K pump to atomic resolution provide a new impetus to investigate molecular determinants governing the binding of Na+ and K+ ions and conformational transitions during the functional cycle. The pump cycle is generally described by the alternating access mechanism, in which the pump toggles between different conformational states, where ions can bind from either the intracellular or the extracellular side. However, important issues concerning the selectivity of the Na/K pump remain to be addressed. In particular, two out of the three binding sites are shared between Na+ and K+ and it is not clear how the protein is able to select K+ over Na+ when it is in the outwardly facing phosphorylated conformation (E2P), and Na+ over K+ when it is in the inwardly facing conformation (E1). In this review article, we will first briefly review the recent advancement in understanding the microscopic mechanism of K+ selectivity in the Na/K pump at the E2·Pi state and then outline the remaining challenges to be addressed about ion selectivity.


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