6ORN

Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch bNAb 10-1074


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.05 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 2.0 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:  
    6ORQ, 6ORN, 6ORP, 6ORO

  • 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 serological responses by vaccination ...

    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

    Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. nussen@rockefeller.edu.



Macromolecules
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
RC1 variant of HIV-1 Env glycoprotein gp41A [auth C], C [auth J], E [auth Q]153Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: env
UniProt
Find proteins for Q2N0S6 (Human immunodeficiency virus 1)
Explore Q2N0S6 
Go to UniProtKB:  Q2N0S6
Protein Feature View
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  • Reference Sequence
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Entity ID: 2
MoleculeChainsSequence LengthOrganismDetailsImage
RC1 variant of HIV-1 Env glycoprotein gp120B [auth G], D [auth K], F [auth R]481Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: env
UniProt
Find proteins for Q2N0S6 (Human immunodeficiency virus 1)
Explore Q2N0S6 
Go to UniProtKB:  Q2N0S6
Protein Feature View
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 3
MoleculeChainsSequence LengthOrganismDetailsImage
10-1074 antibody Fab heavy chainG [auth A], H [auth F], I [auth O]238Homo sapiensMutation(s): 0 
Protein Feature View
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  • Reference Sequence
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Entity ID: 4
MoleculeChainsSequence LengthOrganismDetailsImage
10-1074 antibody Fab light chainJ [auth B], K [auth I], L [auth P]214Homo sapiensMutation(s): 0 
Protein Feature View
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 5
MoleculeChainsChain Length2D DiagramGlycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseBA [auth b], M [auth D], W6N-Glycosylation Oligosaccharides Interaction
Glycosylation Resources
GlyTouCan:  G56014GC
GlyCosmos:  G56014GC
GlyGen:  G56014GC
Entity ID: 6
MoleculeChainsChain Length2D DiagramGlycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseN [auth E], P [auth L], V3N-Glycosylation Oligosaccharides Interaction
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Entity ID: 7
MoleculeChainsChain Length2D DiagramGlycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseO [auth H], U7N-Glycosylation Oligosaccharides Interaction
Glycosylation Resources
GlyTouCan:  G07617FP
GlyCosmos:  G07617FP
GlyGen:  G07617FP
Entity ID: 8
MoleculeChainsChain Length2D DiagramGlycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
AA [auth a], CA [auth c], DA [auth d], FA [auth f], GA [auth g], Q [auth M], R [auth N], S
AA [auth a], CA [auth c], DA [auth d], FA [auth f], GA [auth g], Q [auth M], R [auth N], S, T, X, Y, Z
2N-Glycosylation Oligosaccharides Interaction
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 9
MoleculeChainsChain Length2D DiagramGlycosylation3D Interactions
alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseEA [auth e]6N-Glycosylation Oligosaccharides Interaction
Glycosylation Resources
GlyTouCan:  G34442SS
GlyCosmos:  G34442SS
GlyGen:  G34442SS
Small Molecules
Ligands 1 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
AB [auth K] , BB [auth K] , CB [auth K] , DB [auth Q] , EB [auth Q] , FB [auth Q] , GB [auth R] , HA [auth C] , 
AB [auth K],  BB [auth K],  CB [auth K],  DB [auth Q],  EB [auth Q],  FB [auth Q],  GB [auth R],  HA [auth C],  HB [auth R],  IA [auth C],  IB [auth R],  JA [auth C],  JB [auth R],  KA [auth G],  KB [auth R],  LA [auth G],  MA [auth G],  NA [auth G],  OA [auth G],  PA [auth G],  QA [auth G],  RA [auth G],  SA [auth G],  TA [auth J],  UA [auth J],  VA [auth J],  WA [auth K],  XA [auth K],  YA [auth K],  ZA [auth K]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.05 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 StatesP01 AI100148
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesP50 GM082545-06

Revision History  (Full details and data files)

  • Version 1.0: 2019-06-12
    Type: Initial release
  • Version 1.1: 2019-07-10
    Changes: Data collection, Database references
  • Version 1.2: 2019-12-18
    Changes: Author supporting evidence, Other
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary