6ORO

Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab874NHP


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.9 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation 3D Report Full Report


This is version 1.1 of the entry. See complete history

Literature

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.

Escolano, A.Gristick, H.B.Abernathy, M.E.Merkenschlager, J.Gautam, R.Oliveira, T.Y.Pai, J.West Jr., A.P.Barnes, C.O.Cohen, A.A.Wang, H.Golijanin, J.Yost, D.Keeffe, J.R.Wang, Z.Zhao, P.Yao, K.H.Bauer, J.Nogueira, L.Gao, H.Voll, A.V.Montefiori, D.C.Seaman, M.S.Gazumyan, A.Silva, M.McGuire, A.T.Stamatatos, L.Irvine, D.J.Wells, L.Martin, M.A.Bjorkman, P.J.Nussenzweig, M.C.

(2019) Nature 570: 468-473

  • DOI: 10.1038/s41586-019-1250-z
  • Primary Citation of Related Structures:  

  • PubMed Abstract: 
  • Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serologi ...

    Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.


    Organizational Affiliation

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.,Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.,Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.,Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.,Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. bjorkman@caltech.edu.,Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.,Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. nussen@rockefeller.edu.,Department of Global Health, University of Washington, Seattle, WA, USA.,Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.,David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.,Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA. nussen@rockefeller.edu.,Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.




Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
RC1 variant of HIV-1 Env glycoprotein gp41
A, C, F
153Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: env
Find proteins for Q2N0S6 (Human immunodeficiency virus 1)
Go to UniProtKB:  Q2N0S6
Entity ID: 2
MoleculeChainsSequence LengthOrganismDetails
RC1 variant of HIV-1 Env glycoprotein gp120
B, G, I
481Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: env
Find proteins for Q2N0S6 (Human immunodeficiency virus 1)
Go to UniProtKB:  Q2N0S6
Entity ID: 3
MoleculeChainsSequence LengthOrganismDetails
Ab874NHP antibody Fab heavy chain
D, H, J
254N/AMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.
Entity ID: 4
MoleculeChainsSequence LengthOrganismDetails
Ab874NHP antibody Fab light chain
E, K, L
233N/AMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.
Small Molecules
Ligands 3 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
MAN
Query on MAN

Download SDF File 
Download CCD File 
B, G, I
ALPHA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-PQMKYFCFSA-N
 Ligand Interaction
BMA
Query on BMA

Download SDF File 
Download CCD File 
B, G, I
BETA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-RWOPYEJCSA-N
 Ligand Interaction
NAG
Query on NAG

Download SDF File 
Download CCD File 
A, B, C, F, G, I
N-ACETYL-D-GLUCOSAMINE
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
 Ligand Interaction
Modified Residues  1 Unique
IDChainsTypeFormula2D DiagramParent
UNK
Query on UNK
D, H, J
L-PEPTIDE LINKINGC4 H9 N O2

--

Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.9 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
Software Package:
Software NamePurpose
PHENIXrefinement

Structure Validation

View Full Validation Report or Ramachandran Plots



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious DiseasesUnited StatesP01 AI100148
National Institutes of Health/National Institute of General Medical SciencesUnited StatesP50 GM082545-06

Revision History 

  • Version 1.0: 2019-06-12
    Type: Initial release
  • Version 1.1: 2019-07-10
    Type: Data collection, Database references