Two models of the influenza A M2 channel domain: verification by comparison.
BACKGROUND
The influenza M2 protein is a simple membrane protein, containing a single transmembrane helix. It is representative of a very large family of single-transmembrane helix proteins. The functional protein is a tetramer, with the four transmembrane helices forming a proton-permeable channel across the bilayer. Two independently derived models of the M2 channel domain are compared, in order to assess the success of applying molecular modelling approaches to simple membrane proteins.


RESULTS
The Calpha RSMD between the two models is 1.7 A. Both models are composed of a left-handed bundle of helices, with the helices tilted roughly 15 degrees relative to the (presumed) bilayer normal. The two models 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 residues.


CONCLUSIONS
Independent studies of M2 have converged on the same structural 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 helices are tilted relative to the bilayer normal and form a left-handed bundle. Such convergence suggests that, at least for simple membrane proteins, restraints-directed modelling might yield plausible models worthy of further computational and experimental investigation.
Forrest
L R
LR
Department of Biochemistry, University of Oxford, UK.
DeGrado
W F
WF
Dieckmann
G R
GR
Sansom
M S
MS
D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D017510:Protein Folding; D014763:Viral Matrix Proteins / Q000737:chemistry*; D000086082:Viroporin Proteins
D014763:Viral Matrix Proteins; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins