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| | <StructureSection load='4qkm' size='340' side='right'caption='[[4qkm]], [[Resolution|resolution]] 1.44Å' scene=''> | | <StructureSection load='4qkm' size='340' side='right'caption='[[4qkm]], [[Resolution|resolution]] 1.44Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qkm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QKM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qkm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/udorn/1972(H3N2)) Influenza A virus (A/udorn/1972(H3N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QKM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QKM 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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=OLB:(2S)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLB</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=OLB:(2S)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLB</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=4qkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkm OCA], [https://pdbe.org/4qkm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qkm RCSB], [https://www.ebi.ac.uk/pdbsum/4qkm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qkm ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qk7|4qk7]], [[4qkc|4qkc]], [[4qkl|4qkl]], [[4qk6|4qk6]]</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=4qkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkm OCA], [http://pdbe.org/4qkm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qkm RCSB], [http://www.ebi.ac.uk/pdbsum/4qkm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qkm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/W8PGZ1_9INFA W8PGZ1_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:SAAS00395278] | + | [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: Ph-activated proton channel]]
| + | |
| - | [[Category: Transmembrane alpha helix]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
4qkm is a 1 chain structure with sequence from Influenza A virus (A/udorn/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 matrix 2 (M2) protein from influenza A virus is a proton channel that uses His37 as a selectivity filter. Here we report high-resolution (1.10 A) cryogenic crystallographic structures of the transmembrane domain of M2 at low and high pH. These structures reveal that waters within the pore form hydrogen-bonded networks or "water wires" spanning 17 A from the channel entrance to His37. Pore-lining carbonyl groups are well situated to stabilize hydronium via second-shell interactions involving bridging water molecules. In addition, room temperature crystallographic structures indicate that water becomes increasingly fluid with increasing temperature and decreasing pH, despite the higher electrostatic field. Complementary molecular dynamics simulations reveal a collective switch of hydrogen bond orientations that can contribute to the directionality of proton flux as His37 is dynamically protonated and deprotonated in the conduction cycle.
High-resolution structures of the M2 channel from influenza A virus reveal dynamic pathways for proton stabilization and transduction.,Thomaston JL, Alfonso-Prieto M, Woldeyes RA, Fraser JS, Klein ML, Fiorin G, DeGrado WF Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):14260-5. doi:, 10.1073/pnas.1518493112. Epub 2015 Nov 2. PMID:26578770[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, Alfonso-Prieto M, Woldeyes RA, Fraser JS, Klein ML, Fiorin G, DeGrado WF. High-resolution structures of the M2 channel from influenza A virus reveal dynamic pathways for proton stabilization and transduction. Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):14260-5. doi:, 10.1073/pnas.1518493112. Epub 2015 Nov 2. PMID:26578770 doi:http://dx.doi.org/10.1073/pnas.1518493112
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