Protein Name

Na(+)/H(+) antiporter


Escherichia coli (bacteria)

Biological Context

To control pH exactly at specific values in cells (cytoplasm) is one of the most important things for living beings, because various enzymes can act perfectly only at a specific pH, and the size of cell is also controlled appropriately by the gradient of pH between inner and outer cell. How is pH or the concentration of H+ controlled? It is correctly maintained by “Sodium dependent carrier protein” which is located within the cell membrane. Basically, the cell membrane which separates the outside and inside of the cell is composed of lipid bilayer and does not allow the passage of any charged molecule (ion) including H+, but membrane transport proteins which traverse the cell membrane create the path, thus making it possible to allow ions to pass across the cell membrane, and thus the concentration of various ions which are present both inside and outside the cell is selectively controlled. There are structurally distinguished two kinds of membrane transport proteins: carrier protein and channel protein. Carrier protein has three ways to transfer ions: uniport, symport and antiport. By an antiport system, two kinds of ions are transferred in opposite direction. One of the Na+/H+ antiporter proteins “sodium ion dependent carrier protein” controls the concentration of H+, pH by transferring Na+ and H+ oppositely.

Structure Description


The structure shown here is the Na+/H+ (exchange) antiporter protein NhaA which is present in E.coli or many enterobacteria, under acidic condition by X ray crystallography. The structure under alkaline condition had already been reported by using cryo-electron microscopy at low resolution. NhaA is composed of 12 transmembrane alpha helices. Two helices pass across at the middle of cell membrane, creating a funnel shaped space toward the inner cell. There are negative charged amino acids inside the funnel, making it easy to catch Na+. When the pH of the cell interior is acidic (~pH6.5), the path is closed, whereas under alkaline condition (pH6.5~), the conformation is changed drastically (becomes the active conformation), and the path opens. Na+ is pumped out from cell and H+ is taken up into cell, in this way controlling the pH inside the cell.

"seen_from_membrane" (Fig.1) The molecular structure seen from membrane, including two domains.
"seen_from_cytoplasm" (Fig.2) Seen from cytoplasm side (upper side of fig.1).
"seen_from_cytoplasm" (Fig.3) Two helices cross each other, forming a funnel shaped structure. The red helix and yellow helix are helix IV and XI, respectively. The angle is same as fig.1.

Protein Data Bank (PDB)



  • Hunte, C. Screpanti, E. Venturi, M. Rimon, A. Padan, E. Michel, H.; "Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH."; Nature; (2005) 435:1197-1202 PubMed:15988517.


author: Sachiyo Nomura

Japanese version:PDB:1ZCD