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| | ==Crystal structure of broadly neutralizing anti-HIV-1 antibody 4E10, mutant Npro, with peptide bound== | | ==Crystal structure of broadly neutralizing anti-HIV-1 antibody 4E10, mutant Npro, with peptide bound== |
| - | <StructureSection load='5x08' size='340' side='right' caption='[[5x08]], [[Resolution|resolution]] 1.49Å' scene=''> | + | <StructureSection load='5x08' size='340' side='right'caption='[[5x08]], [[Resolution|resolution]] 1.49Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5x08]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hiv-1 Hiv-1] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X08 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X08 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5x08]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hiv-1 Hiv-1] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X08 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IgG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ENV ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11697 HIV-1])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IgG1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ENV ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11697 HIV-1])</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=5x08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x08 OCA], [http://pdbe.org/5x08 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x08 RCSB], [http://www.ebi.ac.uk/pdbsum/5x08 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x08 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=5x08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x08 OCA], [https://pdbe.org/5x08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x08 RCSB], [https://www.ebi.ac.uk/pdbsum/5x08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x08 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | [[Category: Hiv-1]] | | [[Category: Hiv-1]] |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Caaveiro, J M.M]] | | [[Category: Caaveiro, J M.M]] |
| | [[Category: Nieva, J L]] | | [[Category: Nieva, J L]] |
| Structural highlights
5x08 is a 3 chain structure with sequence from Hiv-1 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , |
| Gene: | IgG1 (HUMAN), ENV (HIV-1) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
The exceptional breadth of broadly neutralizing antibodies (bNAbs) against the membrane-proximal external region (MPER) of the transmembrane protein gp41 makes this class of antibodies an ideal model to design HIV vaccines. From a practical point of view, however, the preparation of vaccines eliciting bNAbs is still a major roadblock that limits their clinical application. Fresh mechanistic insights are necessary to develop more effective strategies. In particular, the function of the unusually long complementarity-determining region three of the heavy chain (CDRH3) of 4E10, an anti-MPER bNAb, is an open question that fascinates researchers in the field. Residues comprising the apex region are dispensable for engagement of the epitope in solution; still, their single mutation profoundly impairs the neutralization capabilities of the antibody. Since this region is very hydrophobic, it has been proposed that the apex is essential for anchoring the antibody to the viral membrane where MPER resides. Herein, we have critically examined this idea using structural, biophysical, biochemical, and cell-based approaches. Our results demonstrate that the apex region is not just a "greasy" spot merely increasing the affinity of the antibody for the membrane. We demonstrate the three-dimensional engagement of the apex region of the CDRH3 with the conglomerate of gp41 epitope and membrane lipids as a means of effective binding and neutralization of the virus. This mechanism of recognition suggests a standard route of antibody ontogeny. Therefore, we need to focus our efforts on recreating a more realistic MPER/lipid immunogen in order to generate more effective anti-HIV-1 vaccines.
Functional Contacts between MPER and the Anti-HIV-1 Broadly Neutralizing Antibody 4E10 Extend into the Core of the Membrane.,Rujas E, Insausti S, Garcia-Porras M, Sanchez-Eugenia R, Tsumoto K, Nieva JL, Caaveiro JM J Mol Biol. 2017 Mar 11. pii: S0022-2836(17)30112-2. doi:, 10.1016/j.jmb.2017.03.008. PMID:28300601[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rujas E, Insausti S, Garcia-Porras M, Sanchez-Eugenia R, Tsumoto K, Nieva JL, Caaveiro JM. Functional Contacts between MPER and the Anti-HIV-1 Broadly Neutralizing Antibody 4E10 Extend into the Core of the Membrane. J Mol Biol. 2017 Mar 11. pii: S0022-2836(17)30112-2. doi:, 10.1016/j.jmb.2017.03.008. PMID:28300601 doi:http://dx.doi.org/10.1016/j.jmb.2017.03.008
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