View source for 6vfl


==BG505-SOSIP model reconstructed by subparticle extraction and refinement from a tetrahedral nanoparticle T33_dn10==
<StructureSection load='6vfl' size='340' side='right'caption='[[6vfl]], [[Resolution|resolution]] 4.14&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vfl]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VFL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.14&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6vfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vfl OCA], [https://pdbe.org/6vfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vfl RCSB], [https://www.ebi.ac.uk/pdbsum/6vfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vfl ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Two-component, self-assembling nanoparticles represent a versatile platform for multivalent presentation of viral antigens. Computational design of protein nanoparticles with differing sizes and geometries enables combination with antigens of choice to test novel multimerization concepts in immunization strategies where the goal is to improve the induction and maturation of neutralizing antibody lineages. Here, we describe detailed antigenic, structural, and functional characterization of computationally designed tetrahedral, octahedral, and icosahedral nanoparticle immunogens displaying trimeric HIV envelope glycoprotein (Env) ectodomains. Env trimers, based on subtype A (BG505) or consensus group M (ConM) sequences and engineered with SOSIP stabilizing mutations, were fused to an underlying trimeric building block of each nanoparticle. Initial screening yielded one icosahedral and two tetrahedral nanoparticle candidates, capable of presenting twenty or four copies of the Env trimer. A number of analyses, including detailed structural characterization by cryo-EM, demonstrated that the nanoparticle immunogens possessed the intended structural and antigenic properties. When the immunogenicity of ConM-SOSIP trimers presented on a two-component tetrahedral nanoparticle or as soluble proteins were compared in rabbits, the two immunogens elicited similar serum antibody binding titers against the trimer component. Neutralizing antibody titers were slightly elevated in the animals given the nanoparticle immunogen and were initially more focused to the trimer apex. Altogether, our findings indicate that tetrahedral nanoparticles can be successfully applied for presentation of HIV Env trimer immunogens; however, the optimal implementation to different immunization strategies remains to be determined.

Structural and functional evaluation of de novo-designed, two-component nanoparticle carriers for HIV Env trimer immunogens.,Antanasijevic A, Ueda G, Brouwer PJM, Copps J, Huang D, Allen JD, Cottrell CA, Yasmeen A, Sewall LM, Bontjer I, Ketas TJ, Turner HL, Berndsen ZT, Montefiori DC, Klasse PJ, Crispin M, Nemazee D, Moore JP, Sanders RW, King NP, Baker D, Ward AB PLoS Pathog. 2020 Aug 11;16(8):e1008665. doi: 10.1371/journal.ppat.1008665., eCollection 2020 Aug. PMID:32780770<ref>PMID:32780770</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Gp120 3D structures|Gp120 3D structures]]
*[[Gp41 3D Structures|Gp41 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Antanasijevic A]]
[[Category: Ward AB]]