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Biophys. J. BioFAST: First Published March 9, 2007. doi:10.1529/biophysj.106.098269
© 2007 by the Biophysical Society.

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BIOPHYSICAL THEORY AND MODELING

The Influence of Protonation States on the Dynamics of the NhaA antiporter from Escherichia coli

Elena Olkhova 1*, Etana Padan 2 and Hartmut Michel 1

1 Max-Planck-Institute of Biophysics
2 Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem

* To whom correspondence should be addressed. E-mail: elena.olkhova{at}mpibp-frankfurt.mpg.de.

Submitted on September 26, 2006
Revised on November 15, 2006
Accepted on 17 January 2007


  Abstract
The crystal structure of NhaA Na,+/H+ antiporter of Escherichia coli has provided a basis to explore the mechanism of Na+ and H+ exchange and its regulation by pH. However, the dynamics and nature of the pH induced changes in the proteins remained unknown. Using molecular mechanics methods, we studied the dynamic behaviour of the hydrogen bonded network in NhaA upon shifting the pH from 4 to 8. The helical regions preserved the general architecture of NhaA throughout the pH change. In contrast, large conformational drifts occurred at pH 8 in the loop regions and an increased flexibility of helix IVp was observed upon the pH shift. A remarkable pH-induced conformational reorganisation was found: at acidic pH helix X is slightly curved, while at alkaline pH it is kinked around residue Lys300. The barrier which exists between the cytoplasmic and periplasmic funnels at low pH is removed and the two funnels are bridged by hydrogen bonds between water molecules and residues located in the TMSs IV/XI assembly and helix X at alkaline pH. In the variant Gly338Ser that lost pH control, a hydrogen bonded chain between Ser338 and Lys300 was found to block the pH induced conformational reorganisation of helix X.

Key Words: hydrogen bonded network, molecular dynamics simulations, sodium proton antiporter, trajectory analysis




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T. Tzubery, A. Rimon, and E. Padan
Structure-based Functional Study Reveals Multiple Roles of Transmembrane Segment IX and Loop VIII-IX in NhaA Na+/H+ Antiporter of Escherichia coli at Physiological pH
J. Biol. Chem., June 6, 2008; 283(23): 15975 - 15987.
[Abstract] [Full Text] [PDF]


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Copyright © 2007 by the Biophysical Society.