Study of ion transport in sodium/proton antiporter proteins by molecular dynamics simulations

POSTER

Abstract

Na+/H+ antiporters serve a vital role in cell homeostasis. New crystallographic X-ray structures for two antiporters exhibit two different conformations: a cytoplasmic-open one (NhaA from Escherichia coli) and a periplasmic-open one (NapA from Thermus thermophilus). NhaA and NapA show low sequence identity but high structural similarity, including a set of highly conserved residues at the sites considered to be vital for transport. The way in which these transporters operate at the molecular scale remains largely undetermined, but using molecular dynamics computer simulations to study the interaction of Na+ ions with the transport proteins affords us new insights. We identify likely ion binding sites in the inward and outward facing conformations, noting that Na+ binding is dependent on the protonation state of a conserved aspartate residue. We also identify a conserved salt bridge that can be destabilized by Na+ binding. Taken together, the combination of structural and simulation data suggests a new model for ion binding and transport for this class of antiporter.

Authors

  • David Dotson

    Arizona State University

  • Benjamin Bloom

    Department of Physics, University of Arizona, Tucson, AZ, National Institute for Materials Science, Tsukuba, Japan, The University of Electro-Communications, Tokyo, Langmuir Laboratory, New Mexico Tech, The University of Arizona, Brigham Young University, Department of Physics Colorado State University, Colorado School of Mines, National Renewable Energy Laboratory, University of Colorado Boulder, Principal Investigator, Graduate Student, Colorado State University, SSRL, SLAC, Department of Chemistry and Biochemistry, Brigham Young University, Department of Physics and Astronomy, Brigham Young University, National Tsing Hua University, Hsinchu, Taiwan, Colorado State Univ, JILA, University of Colorado at Boulder, NIST, JILA, University of Colorado at Boulder, Heinrich-Heine-Universitat, Department of Physics, University of Colorado Denver, Denver, CO 80217, Biomedical Engineering, University of Texas at Austin, Austin, TX, The University Centre in Svalbard, Utah State University, Utah Valley University, New Mexico State University, The George Washington University Nuclear Physics Research Group, Institute for Nuclear Physics at the Johannes Gutenberg University of Mainz, None, Colorado State Engineering Research Center, St. Petersburg Electrotechnical University in Saint Petersburg, Russia, University of California San Diego, Argonne National Laboratory, Los Alamos National Laboratory, Imperial College London, Space Dynamics Lab, Utah State University, Physics and CASS, Utah State University, Department of Chemistry, Colorado State University, Fort Collins, CO 80523, Department of Physics, Colorado State University, Fort Collins, CO 80523, Dept. of Electrical, Computer, and Energy Engineering, University of Colorado at Boulder, Dept. of Physics and Astronomy, University of Denver, CU Boulder, RASEI, NREL, University of Colorado, Rutgers, UTK, Joint Institute for Heavy Ion Research \& ORNL, University of Guelph, Insitituto de Estructura de la Materia, University of Toronto, INFN Laboratori Nazionali del Sud, University of York, University of Surrey, TRIUMF, Simon Frasier University, Universdad de Sevilla, Simon Fraser University, Univ of Utah, Univ of Wyoming, New Mexico Tech, GLOBALFOUNDRIES, IBM Systems and Technology Group, IBM Research Division, Irvine Valley College, University of Colorado - Boulder, Department of Physics, Arizona State University, Tempe, AZ, Department of Physics, New Mexico State University, Las Cruces, NM, Department of Physics, University of Michigan, Flint, MI, High Altitude Observatory, JILA, University of Colorado

  • David Drew

    Stockholm University

  • Alexander Cameron

    University of Warwick

  • Oliver Beckstein

    Arizona State University, Arizona State Univ