M2 Proton Channel: Difference between revisions

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).<ref name="Wu">PMID:12972147 </ref> This allows the RNP to be transported to the nucleus of the cell [wu et al]. Several recent studies have looked at the effects of <scene name='User:Sarah_Henke/Sandbox_1/Amantadine/1'>amantadine</scene><ref name="Stouffer">PMID:18235504 </ref> and <scene name='User:Sarah_Henke/Sandbox_1/Rimantadine/1'>rimantadine</scene><ref name="Schnell">PMID:18235503 </ref> on inhibiting the transfer of protons through the M2 channel.<ref name="Stouffer" /> It has been found that M2 is resistant to these two drugs in 90% of humans, birds and pigs.<ref name="Stouffer" /> Understanding the structure and function of this proton channel is necessary in solving the resistance problem.<ref name="Stouffer" />

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 [Takashi et al]. Circular dichroism spectra has shown the TM domain to form one α-helix  that spans the membrane.<ref name="Wu" /> By analytical ultracentrifugation, the TM domain is found to form <scene name='User:Sarah_Henke/Sandbox_1/Alpha_hlix/1'>α-helical tetramers</scene>[takeuchi et al]. This tetrameric bundle of the TM domain is found by NMR to be tilted by 25-38° from the channel axis [takeuchi et al]. The trameric helices form a left-handed bundle that resembles a truncated cone.<ref name="Stouffer" /> The TM helicies are arranged around the channel pore with an approximate fourfold rotational symmetry [takeuchi et al].