Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2014 Apr;143(4):437-41.
doi: 10.1085/jgp.201411189.

Fishing for holes in transporters: how protons breach the Na/K pump security gates

Donald W Hilgemann  1
Affiliations
Comment

Fishing for holes in transporters: how protons breach the Na/K pump security gates

Donald W Hilgemann. J Gen Physiol. 2014 Apr.
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
A progression of thoughts about ion transport and ion release from ion pumps. Panels A–C were reproduced from the original figures with permission from The Journal of Bioenergetics and Biomembranes, Quarterly Reviews of Biophysics, and Science, respectively. (A) Peter Mitchell’s diagram of an F-type ATPase suggesting that protons diffuse through a long “access channel” along which membrane potential falls off, namely between ATP synthesis/hydrolysis sites and the bulk medium (Mitchell, 1972). For a recent discussion and proposal of an alternative view, see Mulkidjanian (2006). (B) Peter Läuger’s energy diagram of proton translocation by a pump (Läuger, 1979). Microsecond charge–pulse relaxation studies subsequently were used to resolve multiple electrogenic reactions of bacteriorhodopsin that presumably reflect proton association with and dissociation from the carrier (Läuger et al., 1981). For a recent discussion of these principles, see Apell (2004). (C) Reaction scheme suggested by Gadsby et al. (1993) to explain why the extracellular Na concentration and membrane voltage act equivalently on ion flux during pump-mediated Na/Na exchange in squid giant axons. Voltage dependence of the pump was visualized as arising from an access channel on the extracellular side, similar to Peter Mitchell’s original diagram for a proton pump. Nevertheless, analysis of the Na release reactions at higher temporal resolution indicated that more complex interpretations would be required (Hilgemann, 1994; Wuddel and Apell, 1995). (D) A working model of Na release from the Na/K pump based on the study by Vedovato and Gadsby (2014) and recent structural advances (Kanai et al., 2013). From left to right: three Na ions bind with high affinity from the cytoplasmic side, with the binding sites oriented parallel to the membrane surface. Energy of phosphorylation by ATP promotes closure of the cytoplasmic “gate” of the pump and opening of the “gate” to the extracellular side. Release of the first Na ion to the outside involves a complex series of reactions, whereby one Na ion is released from site II and Na ions shift laterally from sites III and I, leaving site III vacant. These events generate the major charge movement of the pump cycle, perhaps involving both the movement of Na ions through electrical field and conformational changes of site III that open a proton pathway to the cytoplasmic side. After site III is vacated, proton passage is enabled from the extracellular space to site III and the cytoplasmic medium, presumably at instants when sites I and II are not occupied by Na. Finally, two K ions replace the two Na ions bound in sites I and II, thereby triggering dephosphorylation and closure of the proton pathway from the extracellular space.
See this image and copyright information in PMC

Comment on

References

    1. Accardi A., Miller C. 2004. Secondary active transport mediated by a prokaryotic homologue of ClC Cl− channels. Nature. 427:803–807 10.1038/nature02314 - DOI - PubMed
    1. Albers R.W. 1967. Biochemical aspects of active transport. Annu. Rev. Biochem. 36:727–756 10.1146/annurev.bi.36.070167.003455 - DOI - PubMed
    1. Apell H.J. 2004. How do P-type ATPases transport ions? Bioelectrochemistry. 63:149–156 10.1016/j.bioelechem.2003.09.021 - DOI - PubMed
    1. Apell H.J., Benz G., Sauerbrunn D. 2011. Proton diet for the sodium pump. Biochemistry. 50:409–418 10.1021/bi101576s - DOI - PubMed
    1. Domaszewicz W., Apell H. 1999. Binding of the third Na+ ion to the cytoplasmic side of the Na,K-ATPase is electrogenic. FEBS Lett. 458:241–246 10.1016/S0014-5793(99)01162-X - DOI - PubMed

Publication types

MeSH terms