M2 Proton Channel

M2 Proton Channel from Influenza A VirusM2 Proton Channel from Influenza A Virus

spinqualitylabelsall models The closed state structure of M2 protein H+ channel by solid state NMR spectroscopy [Stouffer et al, 2008]. Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

BackgroundBackground

The M2 proton channel is a key protein that leads to viral infection [Takeuchi et al]. The M2 proton channel acidifies the viron which allows the viral matrix protein (M1) to disassociate from the ribonucleoprotein (RNP). This allows the RNP to be transported to the nucleus of the cell. Several recent studies have looked at the effects of and on inhibiting the transfer of protons through the M2 channel. It has been found that M2 is resistant to these two drugs in 90% of humans, birds and pigs. Understanding the structure and function of this proton channel is necessary in solving the resistance problem.

StructureStructure

The M2 proton channel from influenza A is 97 amino acid residues and forms a 24-residue N-terminal extracellular domain, a 19-residue trans-membrane domain, and a 54-residue C-terminal cytoplasmic domain [wu et al]. The 19-residue TM domain forms the highly selective proton channel. Circular dichroism spectra has shown the TM domain to form one α-helix that spans the membrane. By analytical ultracentrifugation, the TM domain is found to form This tetrameric bundle of the TM domain is found by NMR to be tilted by 25-38° from the channel axis. The trameric helices form a left-handed bundle that resembles a truncated cone. The TM helicies are arranged around the channel pore with an approximate fourfold rotational symmetry.

Central CavityCentral Cavity

spinqualitylabelsall models High resolution Crystal structure of Transmembrane domain of M2 protein [Stouffer et al, 2008] Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image