5UEM

Crystal structure of 354NC37 Fab in complex with HIV-1 clade AE strain 93TH057 gp120


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.222 

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This is version 2.1 of the entry. See complete history


Literature

Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller.

Freund, N.T.Wang, H.Scharf, L.Nogueira, L.Horwitz, J.A.Bar-On, Y.Golijanin, J.Sievers, S.A.Sok, D.Cai, H.Cesar Lorenzi, J.C.Halper-Stromberg, A.Toth, I.Piechocka-Trocha, A.Gristick, H.B.van Gils, M.J.Sanders, R.W.Wang, L.X.Seaman, M.S.Burton, D.R.Gazumyan, A.Walker, B.D.West, A.P.Bjorkman, P.J.Nussenzweig, M.C.

(2017) Sci Transl Med 9

  • DOI: https://doi.org/10.1126/scitranslmed.aal2144
  • Primary Citation of Related Structures:  
    5UD9, 5UEL, 5UEM

  • PubMed Abstract: 

    Some HIV-1-infected patients develop broad and potent HIV-1 neutralizing antibodies (bNAbs) that when passively transferred to mice or macaques can treat or prevent infection. However, bNAbs typically fail to neutralize coexisting autologous viruses due to antibody-mediated selection against sensitive viral strains. We describe an HIV-1 controller expressing HLA-B57*01 and HLA-B27*05 who maintained low viral loads for 30 years after infection and developed broad and potent serologic activity against HIV-1. Neutralization was attributed to three different bNAbs targeting nonoverlapping sites on the HIV-1 envelope trimer (Env). One of the three, BG18, an antibody directed against the glycan-V3 portion of Env, is the most potent member of this class reported to date and, as revealed by crystallography and electron microscopy, recognizes HIV-1 Env in a manner that is distinct from other bNAbs in this class. Single-genome sequencing of HIV-1 from serum samples obtained over a period of 9 years showed a diverse group of circulating viruses, 88.5% (31 of 35) of which remained sensitive to at least one of the temporally coincident autologous bNAbs and the individual's serum. Thus, bNAb-sensitive strains of HIV-1 coexist with potent neutralizing antibodies that target the virus and may contribute to control in this individual. When administered as a mix, the three bNAbs controlled viremia in HIV-1 YU2 -infected humanized mice. Our finding suggests that combinations of bNAbs may contribute to control of HIV-1 infection.


  • Organizational Affiliation

    Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
clade A/E 93TH057 HIV-1 gp120 coreA [auth G]361Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: HIV-1 Env
UniProt
Find proteins for A0A0M3KKW9 (Human immunodeficiency virus 1)
Explore A0A0M3KKW9 
Go to UniProtKB:  A0A0M3KKW9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0M3KKW9
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
354NC37 Fab Heavy ChainB [auth H]230Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
354NC37 Fab Light ChainC [auth L]213Homo 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
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseD [auth A]2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
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-glucopyranoseE [auth B]5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22768VO
GlyCosmos:  G22768VO
GlyGen:  G22768VO
Entity ID: 6
MoleculeChains Length2D Diagram Glycosylation3D 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-glucopyranoseF [auth C]7N-Glycosylation
Glycosylation Resources
GlyTouCan:  G07617FP
GlyCosmos:  G07617FP
GlyGen:  G07617FP
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.222 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.635α = 90
b = 67.507β = 90
c = 210.664γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Aimlessdata scaling
PHASERphasing
XDSdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-01-10
    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: 2023-10-04
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary