6NNF

Crystal Structure of HIV-1 BG505 SOSIP.664 Prefusion Env Trimer Bound to VRC01 FR3-03 scFv in Complex with Crystallization Chaperones 3H109L Fab and 35O22 scFv at 3.5 Angstrom


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.76 Å
  • R-Value Free: 0.298 
  • R-Value Work: 0.242 
  • R-Value Observed: 0.244 

Starting Models: experimental
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This is version 2.2 of the entry. See complete history


Literature

Improvement of antibody functionality by structure-guided paratope engraftment.

Liu, Q.Lai, Y.T.Zhang, P.Louder, M.K.Pegu, A.Rawi, R.Asokan, M.Chen, X.Shen, C.H.Chuang, G.Y.Yang, E.S.Miao, H.Wang, Y.Fauci, A.S.Kwong, P.D.Mascola, J.R.Lusso, P.

(2019) Nat Commun 10: 721-721

  • DOI: https://doi.org/10.1038/s41467-019-08658-4
  • Primary Citation of Related Structures:  
    6NM6, 6NNF, 6NNJ

  • PubMed Abstract: 

    Broadly neutralizing antibodies (bNAbs) represent a promising alternative to antiretroviral drugs for HIV-1 prevention and treatment. Selected antibodies to the CD4-binding site bolster envelope trimer binding via quaternary contacts. Here, we rationally engraft a new paratope, i.e., the extended heavy-chain framework region 3 (FR3) loop of VRC03, which mediates quaternary interaction, onto several potent bNAbs, enabling them to reach an adjacent gp120 protomer. The interactive quaternary surface is delineated by solving the crystal structure of two FR3 loop-chimeric antibodies. Chimerization enhances the neutralizing activity of several potent bNAbs against a majority of global HIV-1 strains. Compared to unmodified antibodies, chimeric antibodies display lower autoreactivity and prolonged in vivo half-life in huFcRn mice and rhesus macaques. Thus, paratope engraftment may be used to expand the epitope repertory of natural antibodies, improving their functionality for disease prevention and treatment.


  • Organizational Affiliation

    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein gp41A [auth B]153Human immunodeficiency virus 1Mutation(s): 2 
Gene Names: env
UniProt
Find proteins for Q2N0S6 (Human immunodeficiency virus type 1)
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Go to UniProtKB:  Q2N0S6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ2N0S6
Glycosylation
Glycosylation Sites: 2
Sequence Annotations
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
35O22 scFv heavy chainB [auth D]153Homo sapiensMutation(s): 0 
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
35O22 scFv light chainC [auth E]130Homo sapiensMutation(s): 0 
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein gp120D [auth G]481Human immunodeficiency virus 1Mutation(s): 3 
Gene Names: env
UniProt
Find proteins for Q2N0S6 (Human immunodeficiency virus type 1)
Explore Q2N0S6 
Go to UniProtKB:  Q2N0S6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ2N0S6
Glycosylation
Glycosylation Sites: 14
Sequence Annotations
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
3H109L Fab heavy chainE [auth H]244Homo sapiensMutation(s): 0 
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
3H109L Fab light chainF [auth L]217Homo sapiensMutation(s): 0 
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
VRC01 FR3-03 heavy chainG [auth U]142Homo sapiensMutation(s): 0 
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Entity ID: 8
MoleculeChains Sequence LengthOrganismDetailsImage
VRC01 FR3-03 light chainH [auth V]115Homo sapiensMutation(s): 0 
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Oligosaccharides

Help

Entity ID: 9
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-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-glucopyranoseI [auth A]6N-Glycosylation
Glycosylation Resources
GlyTouCan:  G09724ZC
GlyCosmos:  G09724ZC
GlyGen:  G09724ZC
Entity ID: 10
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
J [auth C],
L [auth I],
N [auth K],
O [auth M],
P [auth N],
J [auth C],
L [auth I],
N [auth K],
O [auth M],
P [auth N],
R [auth P],
S [auth Q]
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
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-glucopyranoseK [auth F]5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22768VO
GlyCosmos:  G22768VO
GlyGen:  G22768VO
Entity ID: 12
MoleculeChains Length2D Diagram Glycosylation3D Interactions
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-glucopyranoseM [auth J]4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22573RC
GlyCosmos:  G22573RC
GlyGen:  G22573RC
Entity ID: 13
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-(1-6)-[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-glucopyranoseQ [auth O]10N-Glycosylation
Glycosylation Resources
GlyTouCan:  G40702WU
GlyCosmos:  G40702WU
GlyGen:  G40702WU
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.76 Å
  • R-Value Free: 0.298 
  • R-Value Work: 0.242 
  • R-Value Observed: 0.244 
  • Space Group: P 63
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 130.87α = 90
b = 130.87β = 90
c = 315.19γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PDB_EXTRACTdata extraction
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-02-27
    Type: Initial release
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-10-11
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary
  • Version 2.2: 2024-11-20
    Changes: Structure summary