User:Amy Kerzmann/Sandbox 1

'''Overview of Normal Function:'''

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Influenza A virions bind to host cells via interactions between hemagglutinin and host cell gangliosides (or sialyated proteins), an event which triggers receptor-mediated endocytosis. As the virion-containing endosomes are acidified during the typical maturation process, hemagglutin undergoes a conformational change that leads to membrane fusion. Simultaneously, the M2 channel is activated by the acidic conditions, permitting the flow of proteins from the endosomal lumen to the inside of the viral envelope. This acidification process enhances the rate of viral uncoating that releases viral RNA and other components into the cytosol of the infected cell. In this manner, the function of the M2 channel is essential for viral infectivity.<ref>PMID:19754159</ref>

<applet load='3c9j' size='300' frame='true' align='right' caption='Crystal Structure of the M2 Channel Bound to Amantadine. PDB: 3c9j' />

Channel Structure:

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The M2 proton channel of influenza A is a homotetramer. The central core of this protein is comprised of four transmembrane helices, one from each monomeric subunit. Since all monomers have the same orientation in the membrane, the protein has a four-fold rotational symmetry when viewed from the membrane surface. As a result, each of the channel-lining residues appears as a ring of four identical sidechains. This principle is represented by the conserved <scene name='User:Amy_Kerzmann/Sandbox_1/Conserved_his_and_trp/3'>tryptophan and histidine</scene> residues that function as proton gates within the cavity. <ref>Molecular Biology of the Cell. Alberts, Bruce. New York and London: c2007</ref>

The proton-transport mechanism of the M2 channel is not fully deciphered, but the recent elucidation of a few structures with inhibitors (including amantadine and rimantadine) are providing details that will soon lead to a more complete understanding of this protein. Such developments offer hope that specific treatments for seasonal, as well as pandemic, influenza can soon be developed.

 

<applet load='2rlf' size='300' frame='true' align='right' caption='Insert caption here' />

 

 

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