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==The V27A mutant of influenza A M2 proton channel==
<StructureSection load='2kwx' size='340' side='right'caption='[[2kwx]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2kwx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Udorn/307/1972(H3N2)) Influenza A virus (A/Udorn/307/1972(H3N2))]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KWX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kwx OCA], [https://pdbe.org/2kwx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kwx RCSB], [https://www.ebi.ac.uk/pdbsum/2kwx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kwx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/M2_I72A2 M2_I72A2] Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis. Acidification of the endosome triggers M2 ion channel activity. The influx of protons into virion interior is believed to disrupt interactions between the viral ribonucleoprotein (RNP), matrix protein 1 (M1), and lipid bilayers, thereby freeing the viral genome from interaction with viral proteins and enabling RNA segments to migrate to the host cell nucleus, where influenza virus RNA transcription and replication occur. Also plays a role in viral proteins secretory pathway. Elevates the intravesicular pH of normally acidic compartments, such as trans-Golgi network, preventing newly formed hemagglutinin from premature switching to the fusion-active conformation (By similarity).<ref>PMID:7508997</ref> 
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== Publication Abstract from PubMed ==
The M2 protein of influenza A virus forms a proton-selective channel that is required for viral replication. It is the target of the anti-influenza drugs, amantadine and rimantadine. Widespread drug resistant mutants, however, has greatly compromised the effectiveness of these drugs. Here, we report the solution NMR structure of the highly pathogenic, drug resistant mutant V27A. The structure reveals subtle structural differences from wildtype that maybe linked to drug resistance. The V27A mutation significantly decreases hydrophobic packing between the N-terminal ends of the transmembrane helices, which explains the looser, more dynamic tetrameric assembly. The weakened channel assembly can resist drug binding either by destabilizing the rimantadine-binding pocket at Asp44, in the case of the allosteric inhibition model, or by reducing hydrophobic contacts with amantadine in the pore, in the case of the pore-blocking model. Moreover, the V27A structure shows a substantially increased channel opening at the N-terminal end, which may explain the faster proton conduction observed for this mutant. Furthermore, due to the high quality NMR data recorded for the V27A mutant, we were able to determine the structured region connecting the channel domain to the C-terminal amphipathic helices that was not determined in the wildtype structure. The new structural data show that the amphipathic helices are packed much more closely to the channel domain and provide new insights into the proton transfer pathway.

Solution NMR structure of the V27A drug resistant mutant of influenza A M2 channel.,Pielak RM, Chou JJ Biochem Biophys Res Commun. 2010 Oct 8;401(1):58-63. Epub 2010 Sep 15. PMID:20833142<ref>PMID:20833142</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Ion channels 3D structures|Ion channels 3D structures]]
*[[M2 protein|M2 protein]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Chou JJ]]
[[Category: Pielak RM]]