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| | ==Crystal Structure of the BG505 SOSIP gp140 HIV-1 Env trimer in Complex with the Broadly Neutralizing Fab PGT122== | | ==Crystal Structure of the BG505 SOSIP gp140 HIV-1 Env trimer in Complex with the Broadly Neutralizing Fab PGT122== |
| - | <StructureSection load='4nco' size='340' side='right' caption='[[4nco]], [[Resolution|resolution]] 4.70Å' scene=''> | + | <StructureSection load='4nco' size='340' side='right'caption='[[4nco]], [[Resolution|resolution]] 4.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4nco]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1] and [http://en.wikipedia.org/wiki/Human Human]. The February 2014 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Broadly Neutralizing Antibodies'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2014_2 10.2210/rcsb_pdb/mom_2014_2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NCO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4nco]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. The February 2014 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Broadly Neutralizing Antibodies'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2014_2 10.2210/rcsb_pdb/mom_2014_2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NCO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NCO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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]] 4.7Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jy4|4jy4]], [[4jy5|4jy5]], [[4jy6|4jy6]], [[3j5m|3j5m]]</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=4nco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nco OCA], [https://pdbe.org/4nco PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nco RCSB], [https://www.ebi.ac.uk/pdbsum/4nco PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nco ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">env ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=4nco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nco OCA], [http://pdbe.org/4nco PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nco RCSB], [http://www.ebi.ac.uk/pdbsum/4nco PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nco ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q2N0S6_9HIV1 Q2N0S6_9HIV1]] The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface (By similarity).[RuleBase:RU004292][SAAS:SAAS000328_004_020447] The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves (By similarity).[SAAS:SAAS000328_004_240990] | + | [https://www.uniprot.org/uniprot/Q2N0S6_9HIV1 Q2N0S6_9HIV1] The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface (By similarity).[RuleBase:RU004292][SAAS:SAAS000328_004_020447] The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves (By similarity).[SAAS:SAAS000328_004_240990] |
| | <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 4nco" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4nco" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Gp120 3D structures|Gp120 3D structures]] |
| | + | *[[Gp41 3D Structures|Gp41 3D Structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Broadly Neutralizing Antibodies]] | | [[Category: Broadly Neutralizing Antibodies]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | + | [[Category: Human immunodeficiency virus 1]] |
| | + | [[Category: Large Structures]] |
| | [[Category: RCSB PDB Molecule of the Month]] | | [[Category: RCSB PDB Molecule of the Month]] |
| - | [[Category: Julien, J P]] | + | [[Category: Julien J-P]] |
| - | [[Category: Lyumkis, D]] | + | [[Category: Lyumkis D]] |
| - | [[Category: Stanfield, R L]] | + | [[Category: Stanfield RL]] |
| - | [[Category: Ward, A B]] | + | [[Category: Ward AB]] |
| - | [[Category: Wilson, I A]] | + | [[Category: Wilson IA]] |
| - | [[Category: Broadly neutralizing antibody]]
| + | |
| - | [[Category: Ccr5/cxcr4]]
| + | |
| - | [[Category: Cd4]]
| + | |
| - | [[Category: Gp120]]
| + | |
| - | [[Category: Gp41]]
| + | |
| - | [[Category: Hiv-1 envelope]]
| + | |
| - | [[Category: Membrane fusion]]
| + | |
| - | [[Category: Type-1 membrane fusion glycoprotein trimer]]
| + | |
| - | [[Category: Viral entry]]
| + | |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| - | [[Category: Viral surface]]
| + | |
| Structural highlights
Function
Q2N0S6_9HIV1 The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface (By similarity).[RuleBase:RU004292][SAAS:SAAS000328_004_020447] The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves (By similarity).[SAAS:SAAS000328_004_240990]
Publication Abstract from PubMed
HIV-1 entry into CD4+ target cells is mediated by cleaved envelope glycoprotein (Env) trimers that have been challenging to characterize structurally. Here, we describe the crystal structure at 4.7 A of an antigenically near-native, cleaved, stabilized, soluble Env trimer (termed BG505 SOSIP.664 gp140) in complex with a potent broadly neutralizing antibody, PGT122. The structure shows a pre-fusion state of gp41, the interaction between the component gp120 and gp41 subunits, and how a close association between the gp120 V1/V2/V3 loops stabilizes the trimer apex around the three-fold axis. The complete epitope of PGT122 on the trimer involves gp120 V1, V3 and several surrounding glycans. This trimer structure advances our understanding of how Env functions and is presented to the immune system, and provides a blueprint for structure-based vaccine design.
Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer.,Julien JP, Cupo A, Sok D, Stanfield RL, Lyumkis D, Deller MC, Klasse PJ, Burton DR, Sanders RW, Moore JP, Ward AB, Wilson IA Science. 2013 Oct 31. PMID:24179159[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Julien JP, Cupo A, Sok D, Stanfield RL, Lyumkis D, Deller MC, Klasse PJ, Burton DR, Sanders RW, Moore JP, Ward AB, Wilson IA. Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer. Science. 2013 Oct 31. PMID:24179159 doi:http://dx.doi.org/10.1126/science.1245625
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