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| | ==Nanobody/VHH domain EgA1== | | ==Nanobody/VHH domain EgA1== |
| - | <StructureSection load='4krn' size='340' side='right' caption='[[4krn]], [[Resolution|resolution]] 1.55Å' scene=''> | + | <StructureSection load='4krn' size='340' side='right'caption='[[4krn]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4krn]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KRN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KRN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4krn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KRN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KRN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.553Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4krl|4krl]], [[4krm|4krm]], [[4kro|4kro]], [[4krp|4krp]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4krn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4krn OCA], [http://pdbe.org/4krn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4krn RCSB], [http://www.ebi.ac.uk/pdbsum/4krn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4krn 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=4krn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4krn OCA], [https://pdbe.org/4krn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4krn RCSB], [https://www.ebi.ac.uk/pdbsum/4krn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4krn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4krn" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4krn" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Camelus glama]] | + | [[Category: Lama glama]] |
| - | [[Category: Ferguson, K M]] | + | [[Category: Large Structures]] |
| - | [[Category: Schmitz, K R]] | + | [[Category: Ferguson KM]] |
| - | [[Category: Antibody]] | + | [[Category: Schmitz KR]] |
| - | [[Category: Camelid vh domain]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Nanobody]]
| + | |
| - | [[Category: Vhh domain]]
| + | |
| Structural highlights
Publication Abstract from PubMed
The epidermal growth factor receptor (EGFR) is implicated in human cancers and is the target of several classes of therapeutic agents, including antibody-based drugs. Here, we describe X-ray crystal structures of the extracellular region of EGFR in complex with three inhibitory nanobodies, the variable domains of heavy chain only antibodies (VHH). VHH domains, the smallest natural antigen-binding modules, are readily engineered for diagnostic and therapeutic applications. All three VHH domains prevent ligand-induced EGFR activation, but use two distinct mechanisms. 7D12 sterically blocks ligand binding to EGFR in a manner similar to that of cetuximab. EgA1 and 9G8 bind an epitope near the EGFR domain II/III junction, preventing receptor conformational changes required for high-affinity ligand binding and dimerization. This epitope is accessible to the convex VHH paratope but inaccessible to the flatter paratope of monoclonal antibodies. Appreciating the modes of binding and inhibition of these VHH domains will aid in developing them for tumor imaging and/or cancer therapy.
Structural evaluation of EGFR inhibition mechanisms for nanobodies/VHH domains.,Schmitz KR, Bagchi A, Roovers RC, van Bergen en Henegouwen PM, Ferguson KM Structure. 2013 Jul 2;21(7):1214-24. doi: 10.1016/j.str.2013.05.008. Epub 2013, Jun 20. PMID:23791944[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schmitz KR, Bagchi A, Roovers RC, van Bergen en Henegouwen PM, Ferguson KM. Structural evaluation of EGFR inhibition mechanisms for nanobodies/VHH domains. Structure. 2013 Jul 2;21(7):1214-24. doi: 10.1016/j.str.2013.05.008. Epub 2013, Jun 20. PMID:23791944 doi:10.1016/j.str.2013.05.008
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