1N8Z

Crystal structure of extracellular domain of human HER2 complexed with Herceptin Fab


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.52 Å
  • R-Value Free: 0.284 
  • R-Value Work: 0.222 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Structure of the Extracellular Region of HER2 Alone and in Complex with the Herceptin Fab

Cho, H.-S.Mason, K.Ramyar, K.X.Stanley, A.M.Gabelli, S.B.Denney Jr., D.W.Leahy, D.J.

(2003) Nature 421: 756-760

  • DOI: https://doi.org/10.1038/nature01392
  • Primary Citation of Related Structures:  
    1N8Y, 1N8Z

  • PubMed Abstract: 

    HER2 (also known as Neu, ErbB2) is a member of the epidermal growth factor receptor (EGFR; also known as ErbB) family of receptor tyrosine kinases, which in humans includes HER1 (EGFR, ERBB1), HER2, HER3 (ERBB3) and HER4 (ERBB4). ErbB receptors are essential mediators of cell proliferation and differentiation in the developing embryo and in adult tissues, and their inappropriate activation is associated with the development and severity of many cancers. Overexpression of HER2 is found in 20-30% of human breast cancers, and correlates with more aggressive tumours and a poorer prognosis. Anticancer therapies targeting ErbB receptors have shown promise, and a monoclonal antibody against HER2, Herceptin (also known as trastuzumab), is currently in use as a treatment for breast cancer. Here we report crystal structures of the entire extracellular regions of rat HER2 at 2.4 A and human HER2 complexed with the Herceptin antigen-binding fragment (Fab) at 2.5 A. These structures reveal a fixed conformation for HER2 that resembles a ligand-activated state, and show HER2 poised to interact with other ErbB receptors in the absence of direct ligand binding. Herceptin binds to the juxtamembrane region of HER2, identifying this site as a target for anticancer therapies.


  • Organizational Affiliation

    Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Herceptin Fab (antibody) - light chain214Mus musculusHomo sapiens
This entity is chimeric
Mutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Herceptin Fab (antibody) - heavy chain220Mus musculusHomo sapiens
This entity is chimeric
Mutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Receptor protein-tyrosine kinase erbB-2607Homo sapiensMutation(s): 0 
Gene Names: HER2(erbB2)
EC: 2.7.1.112
UniProt & NIH Common Fund Data Resources
Find proteins for P04626 (Homo sapiens)
Explore P04626 
Go to UniProtKB:  P04626
PHAROS:  P04626
GTEx:  ENSG00000141736 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04626
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.52 Å
  • R-Value Free: 0.284 
  • R-Value Work: 0.222 
  • R-Value Observed: 0.225 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 66.17α = 90
b = 109.77β = 90
c = 175.14γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
REFMACrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-02-18
    Type: Initial release
  • Version 1.1: 2008-05-05
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2014-02-05
    Changes: Source and taxonomy
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.5: 2023-08-16
    Changes: Data collection, Database references, Refinement description, Structure summary