5GGT

PD-L1 in complex with BMS-936559 Fab


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.214 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy

Lee, J.Y.Lee, H.T.Shin, W.Chae, J.Choi, J.Kim, S.H.Lim, H.Won Heo, T.Park, K.Y.Lee, Y.J.Ryu, S.E.Son, J.Y.Lee, J.U.Heo, Y.S.

(2016) Nat Commun 7: 13354-13354

  • DOI: https://doi.org/10.1038/ncomms13354
  • Primary Citation of Related Structures:  
    5GGQ, 5GGR, 5GGS, 5GGT, 5GGU, 5GGV

  • PubMed Abstract: 

    Cancer cells express tumour-specific antigens derived via genetic and epigenetic alterations, which may be targeted by T-cell-mediated immune responses. However, cancer cells can avoid immune surveillance by suppressing immunity through activation of specific inhibitory signalling pathways, referred to as immune checkpoints. In recent years, the blockade of checkpoint molecules such as PD-1, PD-L1 and CTLA-4, with monoclonal antibodies has enabled the development of breakthrough therapies in oncology, and four therapeutic antibodies targeting these checkpoint molecules have been approved by the FDA for the treatment of several types of cancer. Here, we report the crystal structures of checkpoint molecules in complex with the Fab fragments of therapeutic antibodies, including PD-1/pembrolizumab, PD-1/nivolumab, PD-L1/BMS-936559 and CTLA-4/tremelimumab. These complex structures elucidate the precise epitopes of the antibodies and the molecular mechanisms underlying checkpoint blockade, providing useful information for the improvement of monoclonal antibodies capable of attenuating checkpoint signalling for the treatment of cancer.


  • Organizational Affiliation

    Department of Chemistry, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Programmed cell death 1 ligand 1117Homo sapiensMutation(s): 0 
Gene Names: CD274B7H1PDCD1L1PDCD1LG1PDL1
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NZQ7 (Homo sapiens)
Explore Q9NZQ7 
Go to UniProtKB:  Q9NZQ7
PHAROS:  Q9NZQ7
GTEx:  ENSG00000120217 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NZQ7
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
IgG H chainB [auth H]235Homo 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: 3
MoleculeChains Sequence LengthOrganismDetailsImage
IGK@ proteinC [auth L]213Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.214 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.199α = 90
b = 91.555β = 90
c = 164.156γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2016-11-09 
  • Deposition Author(s): Heo, Y.S.

Revision History  (Full details and data files)

  • Version 1.0: 2016-11-09
    Type: Initial release
  • Version 1.1: 2016-11-16
    Changes: Database references
  • Version 1.2: 2024-03-20
    Changes: Data collection, Database references, Derived calculations