6ID4

Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 

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Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01.

Gu, Y.Wong, Y.H.Liew, C.W.Chan, C.E.Z.Murali, T.M.Yap, J.Too, C.T.Purushotorman, K.Hamidinia, M.El Sahili, A.Goh, A.T.H.Teo, R.Z.C.Wood, K.J.Hanson, B.J.Gascoigne, N.R.J.Lescar, J.Vathsala, A.MacAry, P.A.

(2019) Nat Commun 10: 893-893

  • DOI: https://doi.org/10.1038/s41467-019-08790-1
  • Primary Citation of Related Structures:  
    6ID4

  • PubMed Abstract: 

    Our understanding of the conformational and electrostatic determinants that underlie targeting of human leukocyte antigens (HLA) by anti-HLA alloantibodies is principally based upon in silico modelling. Here we provide a biochemical/biophysical and functional characterization of a human monoclonal alloantibody specific for a common HLA type, HLA-A*11:01. We present a 2.4 Å resolution map of the binding interface of this antibody on HLA-A*11:01 and compare the structural determinants with those utilized by T-cell receptor (TCR), killer-cell immunoglobulin-like receptor (KIR) and CD8 on the same molecule. These data provide a mechanistic insight into the paratope-epitope relationship between an alloantibody and its target HLA molecule in a biological context where other immune receptors are concomitantly engaged. This has important implications for our interpretation of serologic binding patterns of anti-HLA antibodies in sensitized individuals and thus, for the biology of human alloresponses.


  • Organizational Affiliation

    Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MHC class I antigen
A, E
276Homo sapiensMutation(s): 0 
Gene Names: HLA-A
UniProt
Find proteins for F6IQY1 (Homo sapiens)
Explore F6IQY1 
Go to UniProtKB:  F6IQY1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupF6IQY1
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin
B, F
100Homo sapiensMutation(s): 0 
Gene Names: B2MCDABP0092HDCMA22P
UniProt & NIH Common Fund Data Resources
Find proteins for P61769 (Homo sapiens)
Explore P61769 
Go to UniProtKB:  P61769
PHAROS:  P61769
GTEx:  ENSG00000166710 
Entity Groups  
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UniProt GroupP61769
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Heavy chainC,
G [auth H]
222Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Light chainD,
H [auth L]
221Homo sapiensMutation(s): 0 
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  • Reference Sequence

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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
peptideI [auth T],
J [auth U]
9Human immunodeficiency virus 1Mutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PEG (Subject of Investigation/LOI)
Query on PEG

Download Ideal Coordinates CCD File 
L [auth A],
N [auth B],
Q [auth E],
S [auth E],
T [auth F]
DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
GOL (Subject of Investigation/LOI)
Query on GOL

Download Ideal Coordinates CCD File 
K [auth A],
M [auth A],
O [auth B],
P [auth D],
R [auth E]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 124.56α = 90
b = 215.33β = 92.96
c = 80.98γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
PHENIXphasing
XDSdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-02-06
    Type: Initial release
  • Version 1.1: 2019-03-06
    Changes: Data collection, Database references, Structure summary
  • Version 2.0: 2020-10-28
    Changes: Advisory, Author supporting evidence, Database references, Polymer sequence, Source and taxonomy, Structure summary
  • Version 2.1: 2023-11-22
    Changes: Data collection, Database references, Refinement description