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| | <StructureSection load='6rx1' size='340' side='right'caption='[[6rx1]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='6rx1' size='340' side='right'caption='[[6rx1]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6rx1]] is a 1 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=6RX1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RX1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rx1]] is a 1 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=6RX1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RX1 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>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERVW-1, ERVWE1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6rx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rx1 OCA], [http://pdbe.org/6rx1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rx1 RCSB], [http://www.ebi.ac.uk/pdbsum/6rx1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rx1 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=6rx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rx1 OCA], [https://pdbe.org/6rx1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rx1 RCSB], [https://www.ebi.ac.uk/pdbsum/6rx1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rx1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SYCY1_HUMAN SYCY1_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. May induce fusion through binding of SLC1A4 and SLC1A5 (PubMed:10708449, PubMed:12050356, PubMed:23492904).<ref>PMID:10708449</ref> <ref>PMID:12050356</ref> <ref>PMID:23492904</ref> Endogenous envelope proteins may have kept, lost or modified their original function during evolution. Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. The surface protein (SU) mediates receptor recognition, while the transmembrane protein (TM) acts as a class I viral fusion protein. The protein may have at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of membranes. | + | [https://www.uniprot.org/uniprot/SYCY1_HUMAN SYCY1_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. May induce fusion through binding of SLC1A4 and SLC1A5 (PubMed:10708449, PubMed:12050356, PubMed:23492904).<ref>PMID:10708449</ref> <ref>PMID:12050356</ref> <ref>PMID:23492904</ref> Endogenous envelope proteins may have kept, lost or modified their original function during evolution. Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. The surface protein (SU) mediates receptor recognition, while the transmembrane protein (TM) acts as a class I viral fusion protein. The protein may have at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of membranes. |
| | <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 6rx1" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6rx1" 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-w]]
| + | |
| - | [[Category: Human placental protein]]
| + | |
| - | [[Category: Membrane fusion]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Syncytin]]
| + | |
| Structural highlights
Function
SYCY1_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. May induce fusion through binding of SLC1A4 and SLC1A5 (PubMed:10708449, PubMed:12050356, PubMed:23492904).[1] [2] [3] Endogenous envelope proteins may have kept, lost or modified their original function during evolution. Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. The surface protein (SU) mediates receptor recognition, while the transmembrane protein (TM) acts as a class I viral fusion protein. The protein may have at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of membranes.
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Blond JL, Lavillette D, Cheynet V, Bouton O, Oriol G, Chapel-Fernandes S, Mandrand B, Mallet F, Cosset FL. An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J Virol. 2000 Apr;74(7):3321-9. PMID:10708449
- ↑ Lavillette D, Marin M, Ruggieri A, Mallet F, Cosset FL, Kabat D. The envelope glycoprotein of human endogenous retrovirus type W uses a divergent family of amino acid transporters/cell surface receptors. J Virol. 2002 Jul;76(13):6442-52. PMID:12050356
- ↑ Sugimoto J, Sugimoto M, Bernstein H, Jinno Y, Schust D. A novel human endogenous retroviral protein inhibits cell-cell fusion. Sci Rep. 2013;3:1462. doi: 10.1038/srep01462. PMID:23492904 doi:http://dx.doi.org/10.1038/srep01462
- ↑ 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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