6CBJ

Crystal Structure of DH270.3 Fab in complex with Man9

  • Classification: IMMUNE SYSTEM
  • Organism(s): Homo sapiens
  • Expression System: Homo sapiens
  • Mutation(s): No 

  • Deposited: 2018-02-03 Released: 2018-02-21 
  • Deposition Author(s): Fera, D., Harrison, S.C.
  • Funding Organization(s): amfAR, National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID), National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.205 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

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

Fera, D.Lee, M.S.Wiehe, K.Meyerhoff, R.R.Piai, A.Bonsignori, M.Aussedat, B.Walkowicz, W.E.Ton, T.Zhou, J.O.Danishefsky, S.Haynes, B.F.Harrison, S.C.

(2018) Nat Commun 9: 1111-1111

  • DOI: https://doi.org/10.1038/s41467-018-03565-6
  • Primary Citation of Related Structures:  
    6CBJ, 6CBP

  • PubMed Abstract: 

    HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide ("Man 9 -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, Man 9 -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.


  • Organizational Affiliation

    Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA. dfera1@swarthmore.edu.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DH270.3 Fab heavy chainA [auth H]238Homo sapiensMutation(s): 0 
UniProt
Find proteins for S6C4S0 (Homo sapiens)
Explore S6C4S0 
Go to UniProtKB:  S6C4S0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupS6C4S0
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DH270.3 Fab light chainB [auth L]216Homo sapiensMutation(s): 0 
UniProt
Find proteins for Q6PJG0 (Homo sapiens)
Explore Q6PJG0 
Go to UniProtKB:  Q6PJG0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6PJG0
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]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-glucopyranoseC [auth A]11N/A
Glycosylation Resources
GlyTouCan:  G60230HH
GlyCosmos:  G60230HH
GlyGen:  G60230HH
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PO4
Query on PO4

Download Ideal Coordinates CCD File 
D [auth H]PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.205 
  • Space Group: I 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 128.087α = 90
b = 128.087β = 90
c = 91.875γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata scaling
PHASERphasing
PDB_EXTRACTdata extraction
Cootmodel building
XDSdata reduction

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
amfARUnited States109502-61-RKVA
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United States1F32-AI-116355
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI100645
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesT32GM007171
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesF30-AI122982
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI127193
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesP41 GM103403

Revision History  (Full details and data files)

  • Version 1.0: 2018-02-21
    Type: Initial release
  • Version 1.1: 2018-02-28
    Changes: Author supporting evidence
  • Version 1.2: 2018-03-28
    Changes: Data collection, Database references
  • Version 1.3: 2018-04-04
    Changes: Data collection, Database references
  • Version 1.4: 2019-04-17
    Changes: Author supporting evidence, Data collection, Database references
  • Version 1.5: 2019-12-18
    Changes: Author supporting evidence
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-10-04
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary