6NFC

BG505 MD64 N332-GT5 SOSIP trimer in complex with BG18-like precursor HMP42 fragmentantigen binding and base-binding RM20A3 fragment antigen binding


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.43 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation 3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses.

Steichen, J.M.Lin, Y.C.Havenar-Daughton, C.Pecetta, S.Ozorowski, G.Willis, J.R.Toy, L.Sok, D.Liguori, A.Kratochvil, S.Torres, J.L.Kalyuzhniy, O.Melzi, E.Kulp, D.W.Raemisch, S.Hu, X.Bernard, S.M.Georgeson, E.Phelps, N.Adachi, Y.Kubitz, M.Landais, E.Umotoy, J.Robinson, A.Briney, B.Wilson, I.A.Burton, D.R.Ward, A.B.Crotty, S.Batista, F.D.Schief, W.R.

(2019) Science 366

  • DOI: 10.1126/science.aax4380
  • Structures With Same Primary Citation

  • PubMed Abstract: 
  • Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy ...

    Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens.


    Organizational Affiliation

    The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.



Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
base-binding RM20A3 fragment antigen binding heavy chain
C, J, K
125Macaca mulattaMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.

Find similar proteins by: Sequence  |  Structure

Entity ID: 2
MoleculeChainsSequence LengthOrganismDetails
base-binding RM20A3 fragment antigen binding light chain
D, M, N
128Macaca mulattaMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.

Find similar proteins by: Sequence  |  Structure

Entity ID: 3
MoleculeChainsSequence LengthOrganismDetails
HIV-1 Env BG505 MD64 N332-GT5 SOSIP gp120
A, E, F
481Human immunodeficiency virus 1Mutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.

Find similar proteins by: Sequence  |  Structure

Entity ID: 4
MoleculeChainsSequence LengthOrganismDetails
HIV-1 Env BG505 MD64 N332-GT5 SOSIP gp41
B, G, I
162Human immunodeficiency virus 1Mutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.

Find similar proteins by: Sequence  |  Structure

Entity ID: 5
MoleculeChainsSequence LengthOrganismDetails
BG18-like precursor HMP42 fragment antigen binding heavy chain
H
128Homo sapiensMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.

Find similar proteins by: Sequence  |  Structure

Entity ID: 6
MoleculeChainsSequence LengthOrganismDetails
BG18-like precursor HMP42 fragment antigen binding light chain
L
108Homo sapiensMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.
Small Molecules
Ligands 3 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download CCD File 
A, B, E, F, G, I
N-ACETYL-D-GLUCOSAMINE
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
 Ligand Interaction
BMA
Query on BMA

Download CCD File 
A, E, F
BETA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-RWOPYEJCSA-N
 Ligand Interaction
MAN
Query on MAN

Download CCD File 
A, E, F
ALPHA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-PQMKYFCFSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.43 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesUM1 AI100663
Bill & Melinda Gates FoundationUnited StatesOPP1115782
Bill & Melinda Gates FoundationUnited StatesOPP1084519

Revision History 

  • Version 1.0: 2019-11-06
    Type: Initial release
  • Version 1.1: 2019-11-13
    Changes: Data collection, Database references
  • Version 1.2: 2019-12-18
    Changes: Author supporting evidence, Database references