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7k3g

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==SARS-CoV-2 Envelope Protein Transmembrane Domain: Pentameric Structure Determined by Solid-State NMR==
==SARS-CoV-2 Envelope Protein Transmembrane Domain: Pentameric Structure Determined by Solid-State NMR==
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<StructureSection load='7k3g' size='340' side='right'caption='[[7k3g]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
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<StructureSection load='7k3g' size='340' side='right'caption='[[7k3g]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[7k3g]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K3G OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7K3G FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7k3g]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K3G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K3G FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">E, 4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</td></tr>
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</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=7k3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k3g OCA], [https://pdbe.org/7k3g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k3g RCSB], [https://www.ebi.ac.uk/pdbsum/7k3g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k3g ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7k3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k3g OCA], [http://pdbe.org/7k3g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7k3g RCSB], [http://www.ebi.ac.uk/pdbsum/7k3g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7k3g ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/VEMP_SARS2 VEMP_SARS2]] Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in the induction of apoptosis.[HAMAP-Rule:MF_04204]
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[https://www.uniprot.org/uniprot/VEMP_SARS2 VEMP_SARS2] Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in the induction of apoptosis.[HAMAP-Rule:MF_04204]
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic. Successful development of vaccines and antivirals against SARS-CoV-2 requires a comprehensive understanding of the essential proteins of the virus. The envelope (E) protein of SARS-CoV-2 assembles into a cation-selective channel that mediates virus budding, release, and host inflammation response. E blockage reduces virus pathogenicity while E deletion attenuates the virus. Here we report the 2.4 A structure and drug-binding site of E's transmembrane (TM) domain, determined using solid-state nuclear magnetic resonance (NMR) spectroscopy. In lipid bilayers that mimic the endoplasmic reticulum Golgi intermediate compartment (ERGIC) membrane, ETM forms a five-helix bundle surrounding a narrow central pore. The middle of the TM segment is distorted from the ideal a-helical geometry due to three regularly spaced phenylalanine residues, which stack within each helix and between neighboring helices. These aromatic interactions, together with interhelical Val and Leu interdigitation, cause a dehydrated pore compared to the viroporins of influenza and HIV viruses. Hexamethylene amiloride and amantadine bind shallowly to polar residues at the N-terminal lumen, while acidic pH affects the C-terminal conformation. These results indicate that SARS-CoV-2 E forms a structurally robust but bipartite channel whose N- and C-terminal halves can interact with drugs, ions and other viral and host proteins semi-independently. This structure establishes the atomic basis for designing E inhibitors as antiviral drugs against SARS-CoV-2.
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An essential protein of the SARS-CoV-2 virus, the envelope protein E, forms a homopentameric cation channel that is important for virus pathogenicity. Here we report a 2.1-A structure and the drug-binding site of E's transmembrane domain (ETM), determined using solid-state NMR spectroscopy. In lipid bilayers that mimic the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane, ETM forms a five-helix bundle surrounding a narrow pore. The protein deviates from the ideal alpha-helical geometry due to three phenylalanine residues, which stack within each helix and between helices. Together with valine and leucine interdigitation, these cause a dehydrated pore compared with the viroporins of influenza viruses and HIV. Hexamethylene amiloride binds the polar amino-terminal lumen, whereas acidic pH affects the carboxy-terminal conformation. Thus, the N- and C-terminal halves of this bipartite channel may interact with other viral and host proteins semi-independently. The structure sets the stage for designing E inhibitors as antiviral drugs.
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Structure and Drug Binding of the SARS-CoV-2 Envelope Protein in Phospholipid Bilayers.,Hong M, Mandala V, McKay M, Shcherbakov A, Dregni A, Kolocouris A Res Sq. 2020 Sep 24. doi: 10.21203/rs.3.rs-77124/v1. PMID:32995764<ref>PMID:32995764</ref>
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Structure and drug binding of the SARS-CoV-2 envelope protein transmembrane domain in lipid bilayers.,Mandala VS, McKay MJ, Shcherbakov AA, Dregni AJ, Kolocouris A, Hong M Nat Struct Mol Biol. 2020 Nov 11. pii: 10.1038/s41594-020-00536-8. doi:, 10.1038/s41594-020-00536-8. PMID:33177698<ref>PMID:33177698</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: 2019-ncov]]
 
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Dregni, A J]]
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[[Category: Severe acute respiratory syndrome coronavirus 2]]
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[[Category: Hong, M]]
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[[Category: Dregni AJ]]
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[[Category: Mandala, V S]]
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[[Category: Hong M]]
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[[Category: McKay, M J]]
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[[Category: Mandala VS]]
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[[Category: Shcherbakov, A S]]
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[[Category: McKay MJ]]
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[[Category: Pentameric ion channel]]
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[[Category: Shcherbakov AS]]
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[[Category: Transmembrane domain]]
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[[Category: Viral protein]]
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[[Category: Viroporin]]
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Current revision

SARS-CoV-2 Envelope Protein Transmembrane Domain: Pentameric Structure Determined by Solid-State NMR

PDB ID 7k3g

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