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Two models of the influenza A M2 channel domain: verification by comparison
L R Forrest1, W F DeGrado, G R Dieckmann
1Department of Biochemistry, University of Oxford, UK.
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.
Insights
Two molecular models of the influenza M2 protein channel domain show remarkable agreement, validating computational approaches for simple membrane proteins. This convergence supports further investigation into these models and their experimental validation.
Area of Science:
- Structural biology
- Biophysics
- Computational modeling
Background:
- Influenza M2 protein is a simple, single-transmembrane helix protein.
- The functional M2 protein forms a tetrameric proton channel across the lipid bilayer.
- It represents a large class of single-transmembrane helix proteins.
Purpose of the Study:
- To compare two independently derived models of the M2 channel domain.
- To assess the efficacy of molecular modeling for simple membrane proteins.
Main Methods:
- Comparative analysis of two structural models.
- Calculation of C-alpha Root Mean Square Deviation (RMSD).
Main Results:
- The two models exhibited a Calpha RMSD of 1.7 Å.
- Both models feature a left-handed helix bundle tilted ~15° relative to the bilayer normal.
- Similar pore radius profiles were observed, with key residues defining the pore cavity and constriction.
Conclusions:
- Independent modeling studies converged on a consistent M2 channel domain structure.
- The structural model aligns with solid-state Nuclear Magnetic Resonance (NMR) data.
- Restraints-directed modeling is a viable approach for generating plausible models of simple membrane proteins.