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J Mol Biol. 2014 Jul 15;426(14):2539-46. doi: 10.1016/j.jmb.2014.05.020. Epub 2014 May 24.

Competition as a way of life for H(+)-coupled antiporters.

Author information

1
Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel. Electronic address: shimon.schuldiner@huji.ac.il.

Abstract

Antiporters are ubiquitous membrane proteins that catalyze obligatory exchange between two or more substrates across a membrane in opposite directions. Some utilize proton electrochemical gradients generated by primary pumps by coupling the downhill movement of one or more protons to the movement of a substrate. Since the direction of the proton gradient usually favors proton movement toward the cytoplasm, their function results in removal of substrates other than protons from the cytoplasm, either into acidic intracellular compartments or out to the medium. H(+)-coupled antiporters play central roles in living organisms, for example, storage of neurotransmitter and other small molecules, resistance to antibiotics, homeostasis of ionic content and more. Biochemical and structural data support a general mechanism for H(+)-coupled antiporters whereby the substrate and the protons cannot bind simultaneously to the protein. In several cases, it was shown that the binding sites overlap, and therefore, there is a direct competition between the protons and the substrate. In others, the "competition" seems to be indirect and it is most likely achieved by allosteric mechanisms. The pKa of one or more carboxyls in the protein must be tuned appropriately in order to ensure the feasibility of such a mechanism. In this review, I discuss in detail the case of EmrE, a multidrug transporter from Escherichia coli and evaluate the information available for other H(+)-coupled antiporters.

KEYWORDS:

coupling mechanism; membrane proteins; multidrug transporters; transport; vesicular neurotransmitter transporters

PMID:
24862284
PMCID:
PMC4072998
DOI:
10.1016/j.jmb.2014.05.020
[Indexed for MEDLINE]
Free PMC Article

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