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HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope.

Daniela Fera | Matthew S Lee | Kevin Wiehe | R Ryan Meyerhoff | Alessandro Piai | Mattia Bonsignori | Baptiste Aussedat | William E Walkowicz | Therese Ton | Jeffrey O Zhou | Samuel Danishefsky | Barton F Haynes | Stephen C Harrison
Nature communications | 2018

HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide ("Man9-V3") for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage ("DH270"), to visualize the epitope on Env and to study how affinity maturation of the lineage proceeded. Unlike many previous V3 mimetics, Man9-V3 encompasses two key features of the V3 region recognized by V3-glycan bnAbs-the conserved GDIR motif and the N332 glycan. In our structure of an antibody fragment of a lineage member, DH270.6, in complex with the V3 glycopeptide, the conformation of the antibody-bound glycopeptide conforms closely to that of the corresponding segment in an intact HIV-1 Env trimer. An additional structure identifies roles for two critical mutations in the development of breadth. The results suggest a strategy for use of a V3 glycopeptide as a vaccine immunogen.

Pubmed ID: 29549260

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NCRR NIH HHS, United States
    Id: S10 RR029205
  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI100645
  • Agency: NIGMS NIH HHS, United States
    Id: P41 GM103403
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIAID NIH HHS, United States
    Id: F30 AI122982
  • Agency: NCI NIH HHS, United States
    Id: P30 CA008748
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI131251
  • Agency: NIH HHS, United States
    Id: S10 OD018164
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007171
  • Agency: NIAID NIH HHS, United States
    Id: F32 AI116355

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GE Healthcare (tool)

RRID:SCR_000004

A commercial antibody supplier and provider of various services.

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ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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GenBank (tool)

RRID:SCR_002760

NIH genetic sequence database that provides annotated collection of all publicly available DNA sequences for almost 280 000 formally described species (Jan 2014) .These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of International Nucleotide Sequence Database Collaboration and daily data exchange with European Nucleotide Archive (ENA) and DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through NCBI Entrez retrieval system, which integrates data from major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of GenBank database are available by FTP.

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Coot (tool)

RRID:SCR_014222

Software for macromolecular model building, model completion and validation, and protein modelling using X-ray data. Coot displays maps and models and allows model manipulations such as idealization, rigid-body fitting, ligand search, Ramachandran plots, non-crystallographic symmetry and more. Source code is available.

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MolProbity (tool)

RRID:SCR_014226

A structure-validation web application which provides an expert-system consultation about the accuracy of a macromolecular structure model, diagnosing local problems and enabling their correction. MolProbity works best as an active validation tool (used as soon as a model is available and during each rebuild/refine loop) and when used for protein and RNA crystal structures, but it may also work well for DNA, ligands and NMR ensembles. It produces coordinates, graphics, and numerical evaluations that integrate with either manual or automated use in systems such as PHENIX, KiNG, or Coot.

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HEK293-F (tool)

RRID:CVCL_6642

Cell line HEK293-F is a Transformed cell line with a species of origin Homo sapiens (Human)

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HEK293T (tool)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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HEK293T (tool)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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