5u64: Difference between revisions
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==Camel nanobody VHH-28== | |||
<StructureSection load='5u64' size='340' side='right'caption='[[5u64]], [[Resolution|resolution]] 1.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5u64]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelus_dromedarius Camelus dromedarius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U64 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U64 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.153Å</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=5u64 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u64 OCA], [https://pdbe.org/5u64 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u64 RCSB], [https://www.ebi.ac.uk/pdbsum/5u64 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u64 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Broadly neutralizing antibodies (bnAbs) against HIV-1 protect from infection and reduce viral load upon therapeutic applications. However no vaccine was able so far to induce bnAbs demanding their expensive biotechnological production. For clinical applications, nanobodies (VHH) derived from heavy chain only antibodies from Camelidae, may be better suited due to their small size, high solubility/stability and extensive homology to human VH3 genes. Here we selected broadly neutralizing nanobodies by phage display after immunization of dromedaries with different soluble trimeric envelope proteins derived from HIV-1 subtype C. We identified 25 distinct VHH families binding trimeric Env, of which 6 neutralized heterologous primary isolates of various HIV-1 subtypes in a standardized in vitro neutralization assay. The complementary neutralization pattern of two selected VHHs in combination covers 19 out of 21 HIV-1 strains from a standardized panel of epidemiologically relevant HIV-1 subtypes. The CD4 binding site was preferentially targeted by the broadly neutralizing VHHs as determined by competition ELISAs and 3D models of VHH-Env complexes derived from negative stain electron microscopy. The nanobodies identified here are excellent candidates for further preclinical/clinical development for prophylactic and therapeutic applications due to their potency and their complementary neutralization patterns covering the majority of epidemiologically relevant HIV-1 subtypes. | |||
Selection of nanobodies with broad neutralizing potential against primary HIV-1 strains using soluble subtype C gp140 envelope trimers.,Koch K, Kalusche S, Torres JL, Stanfield RL, Danquah W, Khazanehdari K, von Briesen H, Geertsma ER, Wilson IA, Wernery U, Koch-Nolte F, Ward AB, Dietrich U Sci Rep. 2017 Aug 21;7(1):8390. doi: 10.1038/s41598-017-08273-7. PMID:28827559<ref>PMID:28827559</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Stanfield | <div class="pdbe-citations 5u64" style="background-color:#fffaf0;"></div> | ||
[[Category: Wilson | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Camelus dromedarius]] | |||
[[Category: Large Structures]] | |||
[[Category: Stanfield RL]] | |||
[[Category: Wilson IA]] | |||
Latest revision as of 13:53, 30 October 2024
Camel nanobody VHH-28Camel nanobody VHH-28
Structural highlights
Publication Abstract from PubMedBroadly neutralizing antibodies (bnAbs) against HIV-1 protect from infection and reduce viral load upon therapeutic applications. However no vaccine was able so far to induce bnAbs demanding their expensive biotechnological production. For clinical applications, nanobodies (VHH) derived from heavy chain only antibodies from Camelidae, may be better suited due to their small size, high solubility/stability and extensive homology to human VH3 genes. Here we selected broadly neutralizing nanobodies by phage display after immunization of dromedaries with different soluble trimeric envelope proteins derived from HIV-1 subtype C. We identified 25 distinct VHH families binding trimeric Env, of which 6 neutralized heterologous primary isolates of various HIV-1 subtypes in a standardized in vitro neutralization assay. The complementary neutralization pattern of two selected VHHs in combination covers 19 out of 21 HIV-1 strains from a standardized panel of epidemiologically relevant HIV-1 subtypes. The CD4 binding site was preferentially targeted by the broadly neutralizing VHHs as determined by competition ELISAs and 3D models of VHH-Env complexes derived from negative stain electron microscopy. The nanobodies identified here are excellent candidates for further preclinical/clinical development for prophylactic and therapeutic applications due to their potency and their complementary neutralization patterns covering the majority of epidemiologically relevant HIV-1 subtypes. Selection of nanobodies with broad neutralizing potential against primary HIV-1 strains using soluble subtype C gp140 envelope trimers.,Koch K, Kalusche S, Torres JL, Stanfield RL, Danquah W, Khazanehdari K, von Briesen H, Geertsma ER, Wilson IA, Wernery U, Koch-Nolte F, Ward AB, Dietrich U Sci Rep. 2017 Aug 21;7(1):8390. doi: 10.1038/s41598-017-08273-7. PMID:28827559[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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