title: M2 proton channel: toward a model of a primitive proton pump.
abstract: Transmembrane proton transfer was essential to early cellular systems in order to transduce energy for metabolic functions. The reliable, efficient and controlled generation of proton gradients became possible only with the emergence of active proton pumps. On the basis of features shared by most modern proton pumps we identify the essential mechanistic steps in active proton transport. Further, we discuss the mechanism of action of a small, transmembrane M2 proton channel from influenza A virus as a model for proton transport in protocells. The M2 channel is a 94-residue long, α-helical tetramer that is activated at low pH and exhibits high selectivity and directionality. A shorter construct, built of transmembrane fragments that are only 24 amino acids in length, exhibits very similar proton transport properties. Molecular dynamics simulations on the microsecond time-scale carried out for the M2 channel provided atomic level details on the activation of the channel in response to protonation of the histidine residue, His37. The pathway of proton conduction is mediated by His37, which accepts and donates protons at different interconverting conformation states when pH is lower than 6.5. The Val27 and Trp41 gates and the salt bridge between Asp44 and Arg45 further enhance the directionality of proton transport. It is argued that the architecture and the mechanism of action similar to that found in the M2 channel might have been the perfect starting point for evolution towards the earliest proton pumps, indicating that active proton transport could have readily emerged from simple, passive proton channels.
authors.affiliation: NASA Ames Research Center, Mail Stop 239-4, Moffett Field, CA, 94035, USA.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Wei
authors.forename: Andrew
authors.initials: A
authors.lastname: Pohorille
mesh_terms: D019418:Evolution, Chemical; D009980:Influenza A virus / Q000737:chemistry*; D008954:Models, Biological; D017494:Proton Pumps / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D017494:Proton Pumps; D014764:Viral Proteins