Two models of the influenza A M2 channel domain: verification by comparison

Background: The influenza M2 protein is a simple membrane protein, containi ng a single transmembrane helix. It is representative of a very large famil y of single-transmembrane helix proteins. The functional protein is a tetra mer, with the four transmembrane helices forming a proton-permeable channel across the bilayer. Two independently derived models of the M2 channel dom ain are compared, in order to assess the success of applying molecular mode lling approaches to simple membrane proteins. Results: The C alpha RSMD between the two models is 1.7 Angstrom. Both mode ls are composed of a left-handed bundle of helices, with the helices tilted roughly 15 degrees relative to the (presumed) bilayer normal. The two mode ls have similar pore radius profiles, with a pore cavity lined by the Ser31 and Gly34 residues and a pore constriction formed by the ring of His37 res idues. Conclusions: Independent studies of M2 have converged on the same structura l model for the channel domain. This model is in agreement with solid state NMR data. In particular, both model and NMR data indicate that the M2 heli ces are tilted relative to the bilayer normal and form a left-handed bundle . Such convergence suggests that, at least for simple membrane proteins, re straints-directed modelling might yield plausible models worthy of further computational and experimental investigation.