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| | ==High resolution crystal structure of transmembrane domain of M2== | | ==High resolution crystal structure of transmembrane domain of M2== |
| - | <StructureSection load='3lbw' size='340' side='right' caption='[[3lbw]], [[Resolution|resolution]] 1.65Å' scene=''> | + | <StructureSection load='3lbw' size='340' side='right'caption='[[3lbw]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lbw]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LBW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LBW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lbw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/H3N2_subtype H3N2 subtype]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LBW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=XYL:D-XYLITOL'>XYL</scene>, <scene name='pdbligand=Z82:4-BROMOBENZOIC+ACID'>Z82</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=XYL:D-XYLITOL'>XYL</scene>, <scene name='pdbligand=Z82:4-BROMOBENZOIC+ACID'>Z82</scene></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=3lbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lbw OCA], [http://pdbe.org/3lbw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lbw RCSB], [http://www.ebi.ac.uk/pdbsum/3lbw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lbw ProSAT]</span></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=3lbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lbw OCA], [https://pdbe.org/3lbw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lbw RCSB], [https://www.ebi.ac.uk/pdbsum/3lbw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lbw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q9YP62_9INFA Q9YP62_9INFA]] 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).[SAAS:SAAS002089_004_400258] | + | [https://www.uniprot.org/uniprot/M2_I97A1 M2_I97A1] 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| | + | *[[Ion channels 3D structures|Ion channels 3D structures]] |
| | *[[M2 protein|M2 protein]] | | *[[M2 protein|M2 protein]] |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Acharya, R]] | + | [[Category: H3N2 subtype]] |
| - | [[Category: DeGrado, W F]] | + | [[Category: Large Structures]] |
| - | [[Category: Polishchuk, A L]] | + | [[Category: Acharya R]] |
| - | [[Category: Host cell membrane]] | + | [[Category: DeGrado WF]] |
| - | [[Category: Hydrogen ion transport]] | + | [[Category: Polishchuk AL]] |
| - | [[Category: Influenza a virus m2 protein]]
| + | |
| - | [[Category: Ionic channel]]
| + | |
| - | [[Category: M2tm]]
| + | |
| - | [[Category: Proton channel]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| - | [[Category: Virion]]
| + | |
| Structural highlights
Function
M2_I97A1 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.
Publication Abstract from PubMed
The M2 proton channel from influenza A virus is an essential protein that mediates transport of protons across the viral envelope. This protein has a single transmembrane helix, which tetramerizes into the active channel. At the heart of the conduction mechanism is the exchange of protons between the His37 imidazole moieties of M2 and waters confined to the M2 bundle interior. Protons are conducted as the total charge of the four His37 side chains passes through 2(+) and 3(+) with a pK(a) near 6. A 1.65 A resolution X-ray structure of the transmembrane protein (residues 25-46), crystallized at pH 6.5, reveals a pore that is lined by alternating layers of sidechains and well-ordered water clusters, which offer a pathway for proton conduction. The His37 residues form a box-like structure, bounded on either side by water clusters with well-ordered oxygen atoms at close distance. The conformation of the protein, which is intermediate between structures previously solved at higher and lower pH, suggests a mechanism by which conformational changes might facilitate asymmetric diffusion through the channel in the presence of a proton gradient. Moreover, protons diffusing through the channel need not be localized to a single His37 imidazole, but instead may be delocalized over the entire His-box and associated water clusters. Thus, the new crystal structure provides a possible unification of the discrete site versus continuum conduction models.
Structure and mechanism of proton transport through the transmembrane tetrameric M2 protein bundle of the influenza A virus.,Acharya R, Carnevale V, Fiorin G, Levine BG, Polishchuk AL, Balannik V, Samish I, Lamb RA, Pinto LH, DeGrado WF, Klein ML Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15075-80. Epub 2010 Aug 5. PMID:20689043[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Acharya R, Carnevale V, Fiorin G, Levine BG, Polishchuk AL, Balannik V, Samish I, Lamb RA, Pinto LH, DeGrado WF, Klein ML. Structure and mechanism of proton transport through the transmembrane tetrameric M2 protein bundle of the influenza A virus. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15075-80. Epub 2010 Aug 5. PMID:20689043 doi:10.1073/pnas.1007071107
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