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| | <StructureSection load='5c02' size='340' side='right'caption='[[5c02]], [[Resolution|resolution]] 1.59Å' scene=''> | | <StructureSection load='5c02' size='340' side='right'caption='[[5c02]], [[Resolution|resolution]] 1.59Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5c02]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C02 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C02 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5c02]] is a 1 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 crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C02 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=SR:STRONTIUM+ION'>SR</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=SR:STRONTIUM+ION'>SR</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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=5c02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c02 OCA], [https://pdbe.org/5c02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c02 RCSB], [https://www.ebi.ac.uk/pdbsum/5c02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c02 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5c02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c02 OCA], [http://pdbe.org/5c02 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c02 RCSB], [http://www.ebi.ac.uk/pdbsum/5c02 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5c02 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/M2_I03A0 M2_I03A0]] 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). | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: DeGrado, W F]] | + | [[Category: DeGrado WF]] |
| - | [[Category: Thomaston, J L]] | + | [[Category: Thomaston JL]] |
| - | [[Category: Drug resistance]]
| + | |
| - | [[Category: Influenza]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| Structural highlights
5c02 is a 1 chain structure with sequence from Influenza A virus (A/Udorn/307/1972(H3N2)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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).[1]
Publication Abstract from PubMed
The M2 protein is a small proton channel found in the influenza A virus that is necessary for viral replication. The M2 channel is the target of a class of drugs called the adamantanes, which block the channel pore and prevent the virus from replicating. In recent decades mutations have arisen in M2 that prevent the adamantanes from binding to the channel pore, with the most prevalent of these mutations being S31N. Here we report the first crystal structure of the S31N mutant crystallized using lipidic cubic phase crystallization techniques and solved to 1.59 A resolution. The Asn31 residues point directly into the center of the channel pore and form a hydrogen-bonded network that disrupts the drug-binding site. Ordered waters in the channel pore form a continuous hydrogen bonding network from Gly34 to His37. This article is protected by copyright. All rights reserved.
Crystal structure of the drug-resistant S31N influenza M2 proton channel.,Thomaston JL, DeGrado WF Protein Sci. 2016 Apr 15. doi: 10.1002/pro.2937. PMID:27082171[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Holsinger LJ, Nichani D, Pinto LH, Lamb RA. Influenza A virus M2 ion channel protein: a structure-function analysis. J Virol. 1994 Mar;68(3):1551-63. PMID:7508997
- ↑ Thomaston JL, DeGrado WF. Crystal structure of the drug-resistant S31N influenza M2 proton channel. Protein Sci. 2016 Apr 15. doi: 10.1002/pro.2937. PMID:27082171 doi:http://dx.doi.org/10.1002/pro.2937
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