ArticleProceedings of the National Academy of Sciences of the United States of America2011
Quaternary structures of HIV Env immunogen exhibit conformational vicissitudes and interface diminution elicited by ligand binding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- The Svedberg Lecture 2017. From nano to micro: the huge dynamic range of the analytical ultracentrifuge for characterising the sizes, shapes and interactions of molecules and assemblies in Biochemistry and Polymer Science.European biophysics journal : EBJ · 2018Article
- Article
- Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5.Journal of virology · 2017Article
- Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops.Scientific reports · 2014Article
- Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions.Science (New York, N.Y.) · 2014Article
- Antigenic and 3D structural characterization of soluble X4 and hybrid X4-R5 HIV-1 Env trimers.Retrovirology · 2014Article
- Alterations in immunodominance of Streptococcus mutans AgI/II: lessons learned from immunomodulatory antibodies.Vaccine · 2014Article
- Linker-extended native cyanovirin-N facilitates PEGylation and potently inhibits HIV-1 by targeting the glycan ligand.PloS one · 2014Article
- A mammalian cell based FACS-panning platform for the selection of HIV-1 envelopes for vaccine development.PloS one · 2014Article
- Allosteric induction of the CD4-bound conformation of HIV-1 Gp120.Retrovirology · 2013Article
- Prefusion structure of trimeric HIV-1 envelope glycoprotein determined by cryo-electron microscopy.Nature structural & molecular biology · 2013Article
- The griffithsin dimer is required for high-potency inhibition of HIV-1: evidence for manipulation of the structure of gp120 as part of the griffithsin dimer mechanism.Antimicrobial agents and chemotherapy · 2013Article
- HIV-1 envelope glycoprotein structure.Current opinion in structural biology · 2013Review
- Dynamic electrophoretic fingerprinting of the HIV-1 envelope glycoprotein.Retrovirology · 2013Article
- Straightforward selection of broadly neutralizing single-domain antibodies targeting the conserved CD4 and coreceptor binding sites of HIV-1 gp120.Journal of virology · 2013Article
- Structure of the arginine methyltransferase PRMT5-MEP50 reveals a mechanism for substrate specificity.PloS one · 2013Article
- Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA.Immunological reviews · 2012Review
- The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin.Molecular pharmaceutics · 2012Article
- Kinetic mechanism for HIV-1 neutralization by antibody 2G12 entails reversible glycan binding that slows cell entry.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
The human immunodeficiency virus envelope protein is the key element mediating entry into host cells. Conformational rearrangement of Env upon binding to the host CD4 receptor and chemokine coreceptor drives membrane fusion. We elucidated the quaternary arrangement of the soluble Env trimeric immunogen o-gp140ΔV2TV1, in both its native (unliganded) and CD4-induced (liganded) states by cryoelectron microscopy and molecular modeling. The liganded conformation was elicited by binding gp140 to the synthetic CD4-mimicking miniprotein CD4m. Upon CD4m binding, an outward domain shift of the three gp120 subunits diminishes gp120-gp41 interactions, whereas a "flat open" concave trimer apex is observed consequent to gp120 tilting away from threefold axis, likely juxtaposing the fusion peptide with the host membrane. Additional features observed in the liganded conformation include rotations of individual gp120 subunits that may release gp41 for N- and C-helix refolding and also may lead to optimal exposure of the elicited coreceptor binding site. Such quaternary arrangements of gp140 lead to the metastable liganded conformation, with putative locations of exposed epitopes contributing to a description of sequential events occurring prior to membrane fusion. Our observations imply a mechanism whereby a soluble Env trimeric construct, as opposed to trimers extracted from virions, may better expose crucial epitopes such as the CD4 binding site and V3, as well as epitopes in the vicinity of gp41, subsequent to conjugation with CD4m. Structural features gleaned from our studies should aid the design of Env-based immunogens for inducement of potent broadly neutralizing antibodies against exposed conformational epitopes.
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