ArticleBiochemistry2013
Thermodynamic signatures of the antigen binding site of mAb 447-52D targeting the third variable region of HIV-1 gp120.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Crystal structures of the human IgD Fab reveal insights into CMolecular immunology · 2023Article
- Higher Affinity Antibodies Bind With Lower Hydration and Flexibility in Large Scale Simulations.Frontiers in immunology · 2022Article
- A site of vulnerability at V3 crown defined by HIV-1 bNAb M4008_N1.Nature communications · 2021Article
- Automated Design by Structure-Based Stabilization and Consensus Repair to Achieve Prefusion-Closed Envelope Trimers in a Wide Variety of HIV Strains.Cell reports · 2020Article
- Development of a 3Mut-Apex-Stabilized Envelope Trimer That Expands HIV-1 Neutralization Breadth When Used To Boost Fusion Peptide-Directed Vaccine-Elicited Responses.Journal of virology · 2020Article
- Computational-guided determination of the functional role of 447-52D long CDRH3.Protein engineering, design & selection : PEDS · 2018Article
- Structural Comparison of Human Anti-HIV-1 gp120 V3 Monoclonal Antibodies of the Same Gene Usage Induced by Vaccination and Chronic Infection.Journal of virology · 2018Article
- Increased Epitope Complexity Correlated with Antibody Affinity Maturation and a Novel Binding Mode Revealed by Structures of Rabbit Antibodies against the Third Variable Loop (V3) of HIV-1 gp120.Journal of virology · 2018Article
- Display of the HIV envelope protein at the yeast cell surface for immunogen development.PloS one · 2018Article
- Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity.Journal of virology · 2017Article
- Article
- Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design.Nature structural & molecular biology · 2016Article
- Structural analysis of a novel rabbit monoclonal antibody R53 targeting an epitope in HIV-1 gp120 C4 region critical for receptor and co-receptor binding.Emerging microbes & infections · 2015Article
- Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env.Nature structural & molecular biology · 2015Article
- Vaccine-induced Human Antibodies Specific for the Third Variable Region of HIV-1 gp120 Impose Immune Pressure on Infecting Viruses.EBioMedicine · 2014Article
- Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The third variable region (V3) of HIV-1 gp120 plays a key role in viral entry into host cells; thus, it is a potential target for vaccine design. Human monoclonal antibody (mAb) 447-52D is one of the most broadly and potently neutralizing anti-V3 mAbs. We further characterized the 447-52D epitope by determining a high-resolution crystal structure of the Fab fragment in complex with a cyclic V3 and interrogated the antigen-antibody interaction by a combination of site-specific mutagenesis, isothermal titration calorimetry (ITC) and neutralization assays. We found that 447-52D's neutralization capability is correlated with its binding affinity and at 25 °C the Gibbs free binding energy is composed of a large enthalpic component and a small favorable entropic component. The large enthalpic contribution is due to (i) an extensive hydrogen bond network, (ii) a π-cation sandwiching the V3 crown apex residue Arg(315), and (iii) a salt bridge between the 447-52D heavy chain residue Asp(H95) and Arg(315). Arg(315) is often harbored by clade B viruses; thus, our data explained why 447-52D preferentially neutralizes clade B viruses. Interrogation of the thermodynamic signatures of residues at the antigen binding interface gives key insights into their contributions in the antigen-antibody interaction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.