ArticleProceedings of the National Academy of Sciences of the United States of America2010
Single-particle cryoelectron microscopy analysis reveals the HIV-1 spike as a tripod structure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- A biophysical perspective on receptor-mediated virus entry with a focus on HIV.Biochimica et biophysica acta. Biomembranes · 2020Review
- Conformational Engineering of HIV-1 Env Based on Mutational Tolerance in the CD4 and PG16 Bound States.Journal of virology · 2019Article
- Antigenic characterization of the human immunodeficiency virus (HIV-1) envelope glycoprotein precursor incorporated into nanodiscs.PloS one · 2017Article
- Article
- A saposin-lipoprotein nanoparticle system for membrane proteins.Nature methods · 2016Article
- Trimerization of the HIV Transmembrane Domain in Lipid Bilayers Modulates Broadly Neutralizing Antibody Binding.Angewandte Chemie (International ed. in English) · 2016Article
- Article
- 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
- Stabilizing the native trimer of HIV-1 Env by destabilizing the heterodimeric interface of the gp41 postfusion six-helix bundle.Journal of virology · 2014Article
- Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Insight derived from molecular dynamics simulations into molecular motions, thermodynamics and kinetics of HIV-1 gp120.PloS one · 2014Article
- 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
- Molecular architecture of the uncleaved HIV-1 envelope glycoprotein trimer.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- HIV-1 variable loop 2 and its importance in HIV-1 infection and vaccine development.Current HIV research · 2013Article
- Inhibition of the HIV-1 spike by single-PG9/16-antibody binding suggests a coordinated-activation model for its three protomeric units.Journal of virology · 2013Article
- The highly conserved layer-3 component of the HIV-1 gp120 inner domain is critical for CD4-required conformational transitions.Journal of virology · 2013Article
- A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1.PloS one · 2013Article
- Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA.Immunological reviews · 2012Review
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HIV-1 spike is a trimer of the transmembrane gp41 and the peripheral gp120 subunit pair. It is activated for virus-cell membrane fusion by binding sequentially to CD4 and to a chemokine receptor. Here we have studied the structural transition of the trimeric spike during the activation process. We solubilized and isolated unliganded and CD4-bound spikes from virus-like particles and used cryoelectron microscopy to reconstruct their 3D structures. In order to increase the yield and stability of the spike, we used an endodomain deleted and gp120-gp41 disulfide-linked variant. The unliganded spike displayed a hollow cage-like structure where the gp120-gp41 protomeric units formed a roof and bottom, and separated lobes and legs on the sides. The tripod structure was verified by fitting the recent atomic core structure of gp120 with intact N- and C-terminal ends into the spike density map. This defined the lobe as gp120 core, showed that the legs contained the polypeptide termini, and suggested the deleted variable loops V1/V2 and V3 to occupy the roof and gp41 the bottom. CD4 binding shifted the roof density peripherally and condensed the bottom density centrally. Fitting with a V3 containing gp120 core suggested that the V1/V2 loops in the roof were displaced laterally and the V3 lifted up, while the core and leg were kept in place. The loop displacements probably prepared the spike for coreceptor interaction and roof opening so that a new fusion-active gp41 structure, assembled at the center of the cage bottom, could reach the target membrane.
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