Proposed partial beta-structures for lac permease and the Na+/H+ antiporter which use similar transport and H+ coupling mechanisms.
Most antiporters, symporters, and transporters have been represented as containing ten to 14 transmembrane helices, primarily on the basis of hydropathy plots. However, multihelix systems provide no obvious mechanism of transport and no simple way of distinguishing substrates. The models of lac permease and the Na+/H+ antiporter presented here postulate that beta-structures are involved in the transport of substrate, and in following this postulate arrive at readily understandable mechanisms for transport and for substrate specificity. The percentage of beta-structures necessary for these models is low enough that it is not in conflict with prior physical evidence for secondary structures. Immunological data also cannot rule these beta-structure mechanisms invalid. In lac permease the new model is obtained by formal representation of the C-terminal amino acids 243-405 as beta-strands. This formal representation nets two interchangeable beta-barrels which provide a simple mechanism for sugar transport. The alternating barrel system may comprise as little as 1/5 the entire permease. In one configuration the barrel forms a pocket with hydrogen bonding residues oriented to the outside of the cell. In the other configuration the barrel forms an analogous pocket oriented towards the inside. Six particular amino acids participate in the substrate hydrogen bonding schemes of both forms, providing a mechanism to shuttle lactose from the outside to the inside or vice versa. A trigger for change of forms which could couple the beta-barrel to H(+)-transport is easily devised, and it involves the apparently critical His322-Glu325 charge relay system. The Na+/H+ antiporter can be organized similarly with an interchanging beta-barrel-beta-clamshell structure attached to 7-transmembrane helices. Charged amino acid sidechains form the basis of an ionic shuttle which is analogous to the lactose shuttle. In this case, too, coupling of Na+ transport to H+ transport may be accomplished by a histidine-glutamate charge relay system.
Radding
W
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Department of Physiology and Biophysics, University of Alabama, Birmingham 35294.
D017920:Antiporters; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000737:chemistry*; D029968:Escherichia coli Proteins; D006859:Hydrogen / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry*; D026901:Membrane Transport Proteins / Q000737:chemistry*; D008956:Models, Chemical; D009004:Monosaccharide Transport Proteins; D012964:Sodium / Q000378:metabolism*; D027981:Symporters
D017920:Antiporters; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C050221:LacY protein, E coli; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; D027981:Symporters; D006859:Hydrogen; C021499:lactose permease; D012964:Sodium