5CEX

Crystal Structure of Fab 32H+109L, a putative precursor of the PGT121 family of potent HIV-1 antibodies


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans.

Garces, F.Lee, J.H.de Val, N.Torrents de la Pena, A.Kong, L.Puchades, C.Hua, Y.Stanfield, R.L.Burton, D.R.Moore, J.P.Sanders, R.W.Ward, A.B.Wilson, I.A.

(2015) Immunity 43: 1053-1063

  • DOI: https://doi.org/10.1016/j.immuni.2015.11.007
  • Primary Citation of Related Structures:  
    5CEX, 5CEY, 5CEZ

  • PubMed Abstract: 

    The high-mannose patch on the HIV-1 envelope (Env) glycoprotein is the epicenter for binding of the potent broadly neutralizing PGT121 family of antibodies, but strategies for generating such antibodies by vaccination have not been defined. We generated structures of inferred antibody intermediates by X-ray crystallography and electron microscopy to elucidate the molecular events that occurred during evolution of this family. Binding analyses revealed that affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan. The overall antibody approach angle to Env was defined very early in the maturation process, yet some variation evolved in the PGT121 family branches that led to differences in glycan specificities in their respective epitopes. Furthermore, we determined a crystal structure of the recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member at 3.0 Å that, in concert with these antibody intermediate structures, provides insights to advance design of HIV vaccine candidates.


  • Organizational Affiliation

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Antibody 9H+3L Fab light chain
A, C
218Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Antibody 9H+3L Fab heavy chain
B, D
236Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
P6G
Query on P6G

Download Ideal Coordinates CCD File 
G [auth B],
K [auth C]
HEXAETHYLENE GLYCOL
C12 H26 O7
IIRDTKBZINWQAW-UHFFFAOYSA-N
PG4
Query on PG4

Download Ideal Coordinates CCD File 
E [auth A],
L [auth C],
M [auth C]
TETRAETHYLENE GLYCOL
C8 H18 O5
UWHCKJMYHZGTIT-UHFFFAOYSA-N
PGE
Query on PGE

Download Ideal Coordinates CCD File 
N [auth C]TRIETHYLENE GLYCOL
C6 H14 O4
ZIBGPFATKBEMQZ-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
F [auth B],
H [auth C],
I [auth C],
J [auth C]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 70.952α = 90
b = 108.726β = 91.35
c = 72.703γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
PHASERphasing
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-12-23
    Type: Initial release
  • Version 1.1: 2016-01-06
    Changes: Database references
  • Version 1.2: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description