PDBsum entry 1zcd

Membrane protein

PDB id: 1zcd

Contents

Protein chains

376 a.a. *

* Residue conservation analysis

PDB id:

1zcd

Name:

Membrane protein

Title:

Crystal structure of the na+/h+ antiporter nhaa

Structure:

Na(+)/h(+) antiporter 1. Chain: a, b. Synonym: sodium/proton antiporter 1. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: nhaa. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

3.45Å R-factor: 0.316 R-free: 0.316

Authors:

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

Key ref:

C.Hunte et al. (2005). Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH. Nature, 435, 1197-1202. PubMed id: 15988517 DOI: 10.1038/nature03692

Date:

11-Apr-05 Release date: 05-Jul-05

Protein chains

P13738  (NHAA_ECOLI) -  Na(+)/H(+) antiporter NhaA from Escherichia coli (strain K12)

Seq: 388 a.a.

Struc: 376 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/nature03692

Nature 435:1197-1202 (2005)

PubMed id: 15988517

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

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

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.

Selected figure(s)

Figure 2.
Figure 2: Overall architecture of NhaA. a, Stereo view of a ribbon representation viewed parallel to the membrane (grey broken lines). The 12 TMSs are labelled with roman numerals; they comprise the following residues: 12 -30 (I), 59 -85 (II), 95 -116 (III), 121 -131 (IVp), 134 -143 (IVc), 150 -175 (V), 182 -200 (VI), 205 -218 (VII), 223 -236 (VIII), 247 -271 (IX), 290 -311 (X), 327 -336 (XIc), 340 -350 (XIp) and 357 -382 (XII). N and C indicate the N and C termini. b, TMSs IV/XI assembly. Helices of the assembly and helix V are shown as cylinders, helix X in ribbon representation. The partial charges of the N and C termini of the short helices are indicated. The orientation of the molecule is indicated with respect to a.

Figure 4.
Figure 4: Structural basis of Na^+/H+ translocation and pH regulation. a, Stereo view of TMSs oriented parallel to the membrane, with the cytoplasmic side at the top. The colour code is as in Fig. 2. Residues whose alterations affect pH regulation12,16,31, apparent K[m] (refs 29, 38) or both29,38 are shown with side chains and labelled blue, black and purple, respectively. The putative 'pH sensor' is encircled. The approximate position of the cytoplasmic passage is marked by red dotted lines connecting Asp 164 with residues lining the funnel entry. b, Close interactions between helix IX and helices IVc and XIp that are important for pH regulation. Van der Waals contacts between side chains are indicated with dotted red lines.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2005, 435, 1197-1202) copyright 2005.

Figures were selected by an automated process.