5VGJ

Crystal Structure of the Human Fab VRC38.01, an HIV-1 V1V2-Directed Neutralizing Antibody Isolated from Donor N90, bound to a scaffolded WITO V1V2 domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.46 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.217 

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This is version 2.1 of the entry. See complete history


Literature

Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that Lacks a Protruding Loop.

Cale, E.M.Gorman, J.Radakovich, N.A.Crooks, E.T.Osawa, K.Tong, T.Li, J.Nagarajan, R.Ozorowski, G.Ambrozak, D.R.Asokan, M.Bailer, R.T.Bennici, A.K.Chen, X.Doria-Rose, N.A.Druz, A.Feng, Y.Joyce, M.G.Louder, M.K.O'Dell, S.Oliver, C.Pancera, M.Connors, M.Hope, T.J.Kepler, T.B.Wyatt, R.T.Ward, A.B.Georgiev, I.S.Kwong, P.D.Mascola, J.R.Binley, J.M.

(2017) Immunity 46: 777-791.e10

  • DOI: https://doi.org/10.1016/j.immuni.2017.04.011
  • Primary Citation of Related Structures:  
    5EWI, 5VGJ

  • PubMed Abstract: 

    Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, which enable them to penetrate the HIV-1 glycan shield. As antibodies with loops of requisite length are created through uncommon recombination events, an alternative mode of apex binding has been sought. Here, we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38.01-11, by using virus-like particles and conformationally stabilized Env trimers as B cell probes. A crystal structure of N90-VRC38.01 with a scaffolded V1V2 revealed a binding mode involving side-chain-to-side-chain interactions that reduced the distance the antibody loop must traverse the glycan shield, thereby facilitating V1V2 binding via a non-protruding loop. The N90-VRC38 lineage thus identifies a solution for V1V2-apex binding that provides a more conventional B cell pathway for vaccine design.


  • Organizational Affiliation

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
1FD6-V1V2-WITOA [auth G]134Human immunodeficiency virus 1Mutation(s): 0 
UniProt
Find proteins for Q5G5U5 (Human immunodeficiency virus 1)
Explore Q5G5U5 
Go to UniProtKB:  Q5G5U5
Entity Groups  
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UniProt GroupQ5G5U5
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
VRC38.01 Fab Heavy ChainB [auth H]236Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
VRC38.01 Fab Light ChainC [auth L]220Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
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  • Reference Sequence
Oligosaccharides

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Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-[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-glucopyranoseD [auth A],
E [auth B]
7N-Glycosylation
Glycosylation Resources
GlyTouCan:  G55220VL
GlyCosmos:  G55220VL
GlyGen:  G55220VL
Entity ID: 5
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-glucopyranoseF [auth C]5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22768VO
GlyCosmos:  G22768VO
GlyGen:  G22768VO
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
G
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.46 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.217 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 106.572α = 90
b = 106.572β = 90
c = 129.857γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data scaling
PDB_EXTRACTdata extraction
HKL-2000data reduction
PHENIXphasing
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-05-31
    Type: Initial release
  • Version 1.1: 2017-11-22
    Changes: Refinement description
  • 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