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| | ==Solution Structure of the trans-membrane domain of the NS2A of dengue virus== | | ==Solution Structure of the trans-membrane domain of the NS2A of dengue virus== |
| - | <StructureSection load='2m0s' size='340' side='right' caption='[[2m0s]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2m0s' size='340' side='right'caption='[[2m0s]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m0s]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M0S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M0S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m0s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_2 Dengue virus 2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M0S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M0S FirstGlance]. <br> |
| - | </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=2m0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m0s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2m0s RCSB], [http://www.ebi.ac.uk/pdbsum/2m0s PDBsum]</span></td></tr> | + | </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=2m0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m0s OCA], [https://pdbe.org/2m0s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m0s RCSB], [https://www.ebi.ac.uk/pdbsum/2m0s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m0s ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q9YKL3_9FLAV Q9YKL3_9FLAV]] Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).[SAAS:SAAS013754_004_099774] | + | [https://www.uniprot.org/uniprot/Q9YKL3_9FLAV Q9YKL3_9FLAV] Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).[SAAS:SAAS013754_004_099774] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2m0s" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Gayen, S]] | + | [[Category: Dengue virus 2]] |
| - | [[Category: Kang, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Membrane protein]] | + | [[Category: Gayen S]] |
| - | [[Category: Nonstructural protein]] | + | [[Category: Kang C]] |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
Q9YKL3_9FLAV Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).[SAAS:SAAS013754_004_099774]
Publication Abstract from PubMed
Flavivirus non-structural protein 2A (NS2A) is a component of viral replication complex, functions in virion assembly, and antagonizes host immune response. Although flavivirus NS2A is known to associate with endoplasmic reticulum (ER) membrane, the detailed topology of this protein has not been determined. Here we report the first topology model of flavivirus NS2A on ER membrane. Using dengue virus (DENV) NS2A as a model, we show that (i) the N-terminal 68 amino acids are located in ER lumen with one segment (amino acids 30-52) that interacts with ER membrane without traversing the lipid bilayer; (ii) amino acids 69 to 209 form five trans-membrane segments, each of which integrally spans the ER membrane; (iii) the C-terminal tail (amino acids 210-218) is located in cytosol. NMR structural analysis showed that the first membrane-spanning segment (amino acids 69-93) consists of two helices separated by a helix "breaker". The helix "breaker" is formed by amino acid P85 and one positively charged residue R84. Functional analysis using replicon and genome-length RNAs of DENV-2 indicates that P85 is not important for viral replication. However, when R84 was substituted with E, the R84E mutation attenuated both viral RNA synthesis and virus production. Remarkably, when R84 was changed to A, the R84A mutation did not affect viral RNA synthesis, but blocked intracellular formation of infectious virions. Collectively, the mutagenesis results demonstrate that NS2A functions in both DENV RNA synthesis and virion assembly/maturation. The topology model of DENV NS2A provides a good starting point to study how flavivirus NS2A modulates viral replication and evasion of host immune response.
Membrane topology and function of dengue virus NS2A protein.,Xie X, Gayen S, Kang C, Yuan Z, Shi PY J Virol. 2013 Feb 13. PMID:23408612[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Xie X, Gayen S, Kang C, Yuan Z, Shi PY. Membrane topology and function of dengue virus NS2A protein. J Virol. 2013 Feb 13. PMID:23408612 doi:http://dx.doi.org/10.1128/JVI.02424-12
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