5UEL

Crystal structure of 354NC102 Fab

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

  • Deposited: 2017-01-02 Released: 2017-02-01 
  • Deposition Author(s): Sievers, S.A., Gristick, H.B., Bjorkman, P.J.
  • Funding Organization(s): 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: 1.60 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.177 

wwPDB Validation   3D Report Full Report


This is version 1.3 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
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
354NC102 Fab Heavy ChainA [auth H]232Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
354NC102 Fab Light ChainB [auth L]216Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.177 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.218α = 90
b = 82.499β = 90
c = 117.211γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Aimlessdata scaling
PHASERphasing
XDSdata scaling

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesP01-AI100148
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesP50-GM082545-06

Revision History  (Full details and data files)

  • Version 1.0: 2017-02-01
    Type: Initial release
  • Version 1.1: 2017-09-13
    Changes: Author supporting evidence
  • Version 1.2: 2017-11-22
    Changes: Refinement description
  • Version 1.3: 2022-04-13
    Changes: Author supporting evidence, Database references