6ISB

crystal structure of human CD226


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.255 
  • R-Value Observed: 0.256 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Binding mode of the side-by-side two-IgV molecule CD226/DNAM-1 to its ligand CD155/Necl-5.

Wang, H.Qi, J.Zhang, S.Li, Y.Tan, S.Gao, G.F.

(2019) Proc Natl Acad Sci U S A 116: 988-996

  • DOI: https://doi.org/10.1073/pnas.1815716116
  • Primary Citation of Related Structures:  
    6ISA, 6ISB, 6ISC

  • PubMed Abstract: 

    Natural killer (NK) cells are important component of innate immunity and also contribute to activating and reshaping the adaptive immune responses. The functions of NK cells are modulated by multiple inhibitory and stimulatory receptors. Among these receptors, the activating receptor CD226 (DNAM-1) mediates NK cell activation via binding to its nectin-like (Necl) family ligand, CD155 (Necl-5). Here, we present a unique side-by-side arrangement pattern of two tandem immunoglobulin V-set (IgV) domains deriving from the ectodomains of both human CD226 (hCD226-ecto) and mouse CD226 (mCD226-ecto), which is substantially different from the conventional head-to-tail arrangement of other multiple Ig-like domain molecules. The hybrid complex structure of mCD226-ecto binding to the first domain of human CD155 (hCD155-D1) reveals a conserved binding interface with the first domain of CD226 (D1), whereas the second domain of CD226 (D2) both provides structural supports for the unique architecture of CD226 and forms direct interactions with CD155. In the absence of the D2 domain, CD226-D1 exhibited substantially reduced binding efficacy to CD155. Collectively, these findings would broaden our knowledge of the interaction between NK cell receptors and the nectin/Necl family ligands, as well as provide molecular basis for the development of CD226-targeted antitumor immunotherapeutics.


  • Organizational Affiliation

    Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences (CAS), 100101 Beijing, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CD226 antigen
A, B, C
232Homo sapiensMutation(s): 0 
Gene Names: CD226DNAM1
UniProt & NIH Common Fund Data Resources
Find proteins for Q15762 (Homo sapiens)
Explore Q15762 
Go to UniProtKB:  Q15762
PHAROS:  Q15762
GTEx:  ENSG00000150637 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15762
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.255 
  • R-Value Observed: 0.256 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.879α = 90
b = 118.492β = 90
c = 123.171γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-12-26
    Type: Initial release
  • Version 1.1: 2019-02-13
    Changes: Data collection, Database references