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| | <StructureSection load='6rx3' size='340' side='right'caption='[[6rx3]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='6rx3' size='340' side='right'caption='[[6rx3]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6rx3]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RX3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RX3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rx3]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RX3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RX3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6rx1|6rx1]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERVFRD-1, ERVFRDE1, UNQ6191/PRO20218 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6rx3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rx3 OCA], [https://pdbe.org/6rx3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rx3 RCSB], [https://www.ebi.ac.uk/pdbsum/6rx3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rx3 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=6rx3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rx3 OCA], [http://pdbe.org/6rx3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rx3 RCSB], [http://www.ebi.ac.uk/pdbsum/6rx3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rx3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SYCY2_HUMAN SYCY2_HUMAN]] This endogenous retroviral envelope protein has retained its original fusogenic properties and participates in trophoblast fusion and the formation of a syncytium during placenta morphogenesis. The interaction with MFSD2A is apparently important for this process (PubMed:18988732).<ref>PMID:18988732</ref> Endogenous envelope proteins may have kept, lost or modified their original function during evolution but this one can still make pseudotypes with MLV, HIV-1 or SIV-1 virions and confer infectivity. Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. The surface protein mediates receptor recognition, while the transmembrane protein anchors the envelope heterodimer to the viral membrane through one transmembrane domain. The other hydrophobic domain, called fusion peptide, mediates fusion of the viral membrane with the target cell membrane (PubMed:14694139).<ref>PMID:14694139</ref> | + | [https://www.uniprot.org/uniprot/SYCY2_HUMAN SYCY2_HUMAN] This endogenous retroviral envelope protein has retained its original fusogenic properties and participates in trophoblast fusion and the formation of a syncytium during placenta morphogenesis. The interaction with MFSD2A is apparently important for this process (PubMed:18988732).<ref>PMID:18988732</ref> Endogenous envelope proteins may have kept, lost or modified their original function during evolution but this one can still make pseudotypes with MLV, HIV-1 or SIV-1 virions and confer infectivity. Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. The surface protein mediates receptor recognition, while the transmembrane protein anchors the envelope heterodimer to the viral membrane through one transmembrane domain. The other hydrophobic domain, called fusion peptide, mediates fusion of the viral membrane with the target cell membrane (PubMed:14694139).<ref>PMID:14694139</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6rx3" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6rx3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Syncytin|Syncytin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Backovic, M]] | + | [[Category: Backovic M]] |
| - | [[Category: Rey, F A]] | + | [[Category: Rey FA]] |
| - | [[Category: Ruigrok, K]] | + | [[Category: Ruigrok K]] |
| - | [[Category: Vaney, M C]] | + | [[Category: Vaney MC]] |
| - | [[Category: Endogenous retrovirus]]
| + | |
| - | [[Category: Herv-frd]]
| + | |
| - | [[Category: Human placental protein]]
| + | |
| - | [[Category: Membrane fusion]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Syncytin]]
| + | |
| Structural highlights
Function
SYCY2_HUMAN This endogenous retroviral envelope protein has retained its original fusogenic properties and participates in trophoblast fusion and the formation of a syncytium during placenta morphogenesis. The interaction with MFSD2A is apparently important for this process (PubMed:18988732).[1] Endogenous envelope proteins may have kept, lost or modified their original function during evolution but this one can still make pseudotypes with MLV, HIV-1 or SIV-1 virions and confer infectivity. Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. The surface protein mediates receptor recognition, while the transmembrane protein anchors the envelope heterodimer to the viral membrane through one transmembrane domain. The other hydrophobic domain, called fusion peptide, mediates fusion of the viral membrane with the target cell membrane (PubMed:14694139).[2]
Publication Abstract from PubMed
The retroviral-envelope-derived proteins syncytin-1 and -2 (syn1 and syn2) drive placentation in humans by forming a syncytiotophoblast - a structure allowing for an exchange interface between maternal and fetal blood during pregnancy. Despite their essential role, little is known about the molecular mechanism underlying the syncytins' function. We report here the X-ray structures of the syn1 and syn2 transmembrane subunit ectodomains, featuring a 6-helix bundle (6HB) typical of the post-fusion state of gamma-retrovirus and filovirus fusion proteins. Contrary to the filoviruses, for which the fusion glycoprotein was crystallized both in the post-fusion and in the spring-loaded pre-fusion form, the highly unstable nature of the syncytins' pre-fusion form has precluded structural studies. We undertook a proline-scanning approach searching for regions in the syn1 6HB central helix that tolerate the introduction of helix-breaker residues and still fold correctly in the pre-fusion form. We found that there is indeed such a region, located two alpha-helical turns downstream a stutter in the central coiled-coil helix - precisely where the breaks of the spring-loaded helix of the filoviruses map. These mutants were fusion-inactive as they cannot form the 6HB, similar to the "SOSIP" mutant of HIV Env that allowed the high-resolution structural characterization of its labile pre-fusion form. These results now open a new window of opportunity to engineer more stable variants of the elusive pre-fusion trimer of the syncytins and other gamma-retroviruses envelope proteins for structural characterization.
X-ray structures of the post-fusion 6-helix bundle of the human syncytins and their functional implications.,Ruigrok K, Vaney MC, Buchrieser J, Baquero E, Hellert J, Baron B, England P, Schwartz O, Rey FA, Backovic M J Mol Biol. 2019 Nov 8. pii: S0022-2836(19)30616-3. doi:, 10.1016/j.jmb.2019.10.020. PMID:31711961[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Esnault C, Priet S, Ribet D, Vernochet C, Bruls T, Lavialle C, Weissenbach J, Heidmann T. A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2. Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17532-7. doi:, 10.1073/pnas.0807413105. Epub 2008 Nov 6. PMID:18988732 doi:http://dx.doi.org/10.1073/pnas.0807413105
- ↑ Blaise S, Ruggieri A, Dewannieux M, Cosset FL, Heidmann T. Identification of an envelope protein from the FRD family of human endogenous retroviruses (HERV-FRD) conferring infectivity and functional conservation among simians. J Virol. 2004 Jan;78(2):1050-4. PMID:14694139
- ↑ Ruigrok K, Vaney MC, Buchrieser J, Baquero E, Hellert J, Baron B, England P, Schwartz O, Rey FA, Backovic M. X-ray structures of the post-fusion 6-helix bundle of the human syncytins and their functional implications. J Mol Biol. 2019 Nov 8. pii: S0022-2836(19)30616-3. doi:, 10.1016/j.jmb.2019.10.020. PMID:31711961 doi:http://dx.doi.org/10.1016/j.jmb.2019.10.020
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