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Author(s): Carola Hunte (corresponding author) [1]; Emanuela Screpanti [1]; Miro Venturi [1]; Abraham Rimon [2]; Etana Padan (corresponding author) [2]; Hartmut Michel (corresponding author) [1] Regulation of intracellular pH, cellular [...]

Author(s): Peter D. Kwong (corresponding author) [1, 2]; Michael L. Doyle [3, 4]; David J. Casper [3]; Claudia Cicala [5]; Stephanie A. Leavitt [6]; Shahzad Majeed [1, 2]; Tavis D. [...]

The control by Na+/H+ antiporters of sodium/proton concentration and cell volume is crucial for the viability of all cells. Adaptation to high salinity and/or extreme pH in plants and bacteria or in human heart muscles requires the action of Na+/H+ antiporters. Their activity is tightly controlled by pH. Here we present the crystal structure of pH-downregulated NhaA, the main antiporter of Escherichia coli and many enterobacteria. A negatively charged ion funnel opens to the cytoplasm and ends in the middle of the membrane at the putative ion-binding site. There, a unique assembly of two pairs of short helices connected by crossed, extended chains creates a balanced electrostatic environment. We propose that the binding of charged substrates causes an electric imbalance, inducing movements, that permit a rapid alternating-access mechanism. This ion-exchange machinery is regulated by a conformational change elicited by a pH signal perceived at the entry to the cytoplasmic funnel. [ABSTRACT FROM AUTHOR]