Nature. 2005 Jun 30;435(7046):1197-202.

Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH.

Hunte C, Screpanti E, Venturi M, Rimon A, Padan E, Michel H.

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Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, D-60438 Frankfurt, Germany.

Abstract

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.

PMID:: 15988517; [PubMed - indexed for MEDLINE]

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Cited by 70 PubMed Central articles

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Structures reported by this article

Crystal Structure Of The Na+H+ ANTIPORTER NHAA

PDB: 1ZCD

Source: Escherichia coli

Method: X-Ray Diffraction

Resolution: 3.45 Å

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