6CUE

Cryo-EM structure at 4.0 A resolution of vaccine-elicited antibody vFP7.04 in complex with HIV-1 Env BG505 DS-SOSIP, and antibodies VRC03 and PGT122


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.00 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

Complete functional mapping of infection- and vaccine-elicited antibodies against the fusion peptide of HIV.

Dingens, A.S.Acharya, P.Haddox, H.K.Rawi, R.Xu, K.Chuang, G.Y.Wei, H.Zhang, B.Mascola, J.R.Carragher, B.Potter, C.S.Overbaugh, J.Kwong, P.D.Bloom, J.D.

(2018) PLoS Pathog 14: e1007159-e1007159

  • DOI: https://doi.org/10.1371/journal.ppat.1007159
  • Primary Citation of Related Structures:  
    6CUE, 6CUF

  • PubMed Abstract: 

    Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env's fusion peptide.


  • Organizational Affiliation

    Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein gp120A [auth c],
B [auth 2],
C
473Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: env
UniProt
Find proteins for Q2N0S6 (Human immunodeficiency virus 1)
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Go to UniProtKB:  Q2N0S6
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UniProt GroupQ2N0S6
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein gp41D [auth 1],
K [auth D],
R [auth d]
153Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: env
UniProt
Find proteins for Q2N0S7 (Human immunodeficiency virus 1)
Explore Q2N0S7 
Go to UniProtKB:  Q2N0S7
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Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ2N0S7
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
vFP7.04 Heavy chainE [auth 3],
L [auth H],
S [auth h]
118Mus musculusMutation(s): 0 
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
vFP7.04 light chainF [auth 4],
M [auth L],
T [auth l]
112Mus musculusMutation(s): 0 
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
PGT122 heavy ChainG [auth 5],
N [auth M],
U [auth m]
132Homo sapiensMutation(s): 0 
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
PGT122 Light chainH [auth 6],
O [auth N],
V [auth n]
107Homo sapiensMutation(s): 0 
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
VRC03 Heavy chainI [auth 7],
P [auth Q],
W [auth q]
129Homo sapiensMutation(s): 0 
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Entity ID: 8
MoleculeChains Sequence LengthOrganismDetailsImage
VRC03 light chainJ [auth 8],
Q [auth R],
X [auth r]
102Homo sapiensMutation(s): 0 
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Oligosaccharides

Help

Entity ID: 9
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
BA [auth F],
BB [auth t],
CA [auth G],
CB [auth u],
EA [auth J],
BA [auth F],
BB [auth t],
CA [auth G],
CB [auth u],
EA [auth J],
EB [auth w],
FA [auth K],
FB [auth x],
HA [auth P],
HB [auth z],
JA [auth T],
JB [auth 9],
LA [auth V],
OA [auth Y],
PA [auth Z],
RA [auth b],
SA [auth e],
UA [auth g],
WA [auth j],
Y [auth A],
YA [auth o]
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 10
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
AA [auth E],
AB [auth s],
GA [auth O],
GB [auth y],
MA [auth W],
AA [auth E],
AB [auth s],
GA [auth O],
GB [auth y],
MA [auth W],
NA [auth X],
TA [auth f],
Z [auth B],
ZA [auth p]
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Entity ID: 11
MoleculeChains Length2D Diagram Glycosylation3D Interactions
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-glucopyranoseDA [auth I],
DB [auth v],
QA [auth a]
5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22768VO
GlyCosmos:  G22768VO
GlyGen:  G22768VO
Entity ID: 12
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-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-glucopyranoseIA [auth S],
IB [auth 0],
VA [auth i]
5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42227JK
GlyCosmos:  G42227JK
GlyGen:  G42227JK
Entity ID: 13
MoleculeChains Length2D Diagram Glycosylation3D Interactions
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-glucopyranoseKA [auth U],
KB [auth AA],
XA [auth k]
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G81315DD
GlyCosmos:  G81315DD
GlyGen:  G81315DD
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.00 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONcryoSPARC
MODEL REFINEMENTPHENIX1.13-2998-000

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-07-11
    Type: Initial release
  • Version 1.1: 2018-07-18
    Changes: Data collection, Database references
  • Version 1.2: 2018-10-03
    Changes: Data collection, Refinement description
  • Version 1.3: 2019-12-18
    Changes: Other
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Other, Structure summary