Common themes and problems of bioenergetics and voltage-gated proton channels

The existence of a proton-selective pathway through a protein is a common feature of voltage-gated proton channels and a number of molecules that play pivotal roles in bioenergetics. Although the functions and structures of these molecules are quite diverse, the proton conducting pathways share a number of fundamental properties. Conceptual parallels include the translocation by hydrogen-bended chain mechanisms, problems of supply and demand, equivalence of chemical and electrical proton gradients, proton wells, alternating access sites, pK(a) changes induced by protein conformational change, and heavy metal participation in proton transfer processes. An archetypal mechanism involves input and output proton pathways (hydrogen-bonded chains) joined by a regulatory site that switches the accessibility of the bound proton from one 'channel' to the other, by means of a pK(a) change, molecular movement, or both. Although little is known about the structure of voltage-gated proton channels, they appear to share many of these features. Evidently, nature has devised a limited number of mechanisms to accomplish various design strategies, and these fundamental mechanisms are repeated with minor variation in many superficially disparate molecules. (C) 2000 Elsevier Science B.V. All rights reserved.