Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH.
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.
Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, D-60438 Frankfurt, Germany.
Carola
C
Hunte
Emanuela
E
Screpanti
Miro
M
Venturi
Abraham
A
Rimon
Etana
E
Padan
Hartmut
H
Michel
D001665:Binding Sites; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D011522:Protons; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055672:Static Electricity; D013329:Structure-Activity Relationship
D029968:Escherichia coli Proteins; C102839:NhaA protein, E coli; D011522:Protons; D017923:Sodium-Hydrogen Exchangers; D006859:Hydrogen; D012964:Sodium