5TLK

COMPLEX BETWEEN HUMAN CD27 AND FAB FRAGMENTS OF ANTIBODIES M2177 AND H2191


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.214 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Epitope-dependent mechanisms of CD27 neutralization revealed by X-ray crystallography.

Obmolova, G.Teplyakov, A.Malia, T.J.Wunderler, N.Kwok, D.Barone, L.Sweet, R.Ort, T.Scully, M.Gilliland, G.L.

(2017) Mol Immunol 83: 92-99

  • DOI: https://doi.org/10.1016/j.molimm.2017.01.005
  • Primary Citation of Related Structures:  
    5TLJ, 5TLK

  • PubMed Abstract: 

    CD27 is a T and B cell co-stimulatory protein of the TNF receptor superfamily dependent on the availability of the TNF-like ligand CD70. Two anti-CD27 neutralizing monoclonal antibodies were obtained from mouse hybridoma and subsequently humanized and optimized for binding the target. The two antibodies are similar in terms of their CD27-binding affinity and ability to block NF-κB signaling, however their clearance rates in monkeys are very different. The pharmacokinetics profiles could be epitope dependent. To identify the epitopes, we determined the crystal structure of the ternary complex between CD27 and the Fab fragments of these non-competing antibodies. The structure reveals the binding modes of the antibodies suggesting that their mechanisms of action are distinctly different and provides a possible explanation of the in vivo data.


  • Organizational Affiliation

    Janssen Research and Development, LLC, 1400 McKean Road, Spring House, PA 19477, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
M2177 LIGHT CHAIN
A, E
218Mus musculusHomo sapiens
This entity is chimeric
Mutation(s): 0 
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
M2177 HEAVY CHAIN
B, F
229Mus musculusHomo sapiens
This entity is chimeric
Mutation(s): 0 
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
H2191 LIGHT CHAIN
C, G
218Mus musculusHomo sapiens
This entity is chimeric
Mutation(s): 0 
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
H2191 HEAVY CHAIN
D, H
226Mus musculusHomo sapiens
This entity is chimeric
Mutation(s): 0 
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
CD27 antigenI [auth X],
J [auth Y]
109Homo sapiensMutation(s): 0 
Gene Names: CD27TNFRSF7
UniProt & NIH Common Fund Data Resources
Find proteins for P26842 (Homo sapiens)
Explore P26842 
Go to UniProtKB:  P26842
PHAROS:  P26842
GTEx:  ENSG00000139193 
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UniProt GroupP26842
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  • Reference Sequence
Oligosaccharides

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Entity ID: 6
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseK [auth I],
L [auth J]
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PCA
Query on PCA
B, F
L-PEPTIDE LINKINGC5 H7 N O3GLN
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.214 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 139.71α = 90
b = 52.96β = 109.52
c = 140.6γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-02-08
    Type: Initial release
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Polymer sequence, Structure summary
  • Version 2.1: 2023-10-04
    Changes: Data collection, Database references, Refinement description, Structure summary