2KS1

Heterodimeric association of Transmembrane domains of ErbB1 and ErbB2 receptors Enabling Kinase Activation


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 12 
  • Selection Criteria: target function 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Spatial Structure of the Transmembrane Domain Heterodimer of ErbB1 and ErbB2 Receptor Tyrosine Kinases

Mineev, K.S.Bocharov, E.V.Pustovalova, Y.E.Bocharova, O.V.Chupin, V.V.Arseniev, A.S.

(2010) J Mol Biol 

  • DOI: https://doi.org/10.1016/j.jmb.2010.05.016
  • Primary Citation of Related Structures:  
    2KS1

  • PubMed Abstract: 

    Growth factor receptor tyrosine kinases of the ErbB family play a significant role in vital cellular processes and various cancers. During signal transduction across plasma membrane, ErbB receptors are involved in lateral homodimerization and heterodimerization with proper assembly of their extracellular single-span transmembrane (TM) and cytoplasmic domains. The ErbB1/ErbB2 heterodimer appears to be the strongest and most potent inducer of cellular transformation and mitogenic signaling compared to other ErbB homodimers and heterodimers. Spatial structure of the heterodimeric complex formed by TM domains of ErbB1 and ErbB2 receptors embedded into lipid bicelles was obtained by solution NMR. The ErbB1 and ErbB2 TM domains associate in a right-handed alpha-helical bundle through their N-terminal double GG4-like motif T(648)G(649)X(2)G(652)A(653) and glycine zipper motif T(652)X(3)S(656)X(3)G(660), respectively. The described heterodimer conformation is believed to support the juxtamembrane and kinase domain configuration corresponding to the receptor active state. The capability for multiple polar interactions, along with hydrogen bonding between TM segments, correlates with the observed highest affinity of the ErbB1/ErbB2 heterodimer, implying an important contribution of the TM helix-helix interaction to signal transduction.


  • Organizational Affiliation

    Division of Structural Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, ul. Miklukho-Maklaya, 16/10, Moscow 117997, Russia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Receptor tyrosine-protein kinase erbB-244Homo sapiensMutation(s): 0 
Gene Names: ERBB2HER2NEUNGL
EC: 2.7.10.1
Membrane Entity: Yes 
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
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Epidermal growth factor receptor44Homo sapiensMutation(s): 0 
Gene Names: EGFRERBB1
EC: 2.7.10.1
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P00533 (Homo sapiens)
Explore P00533 
Go to UniProtKB:  P00533
PHAROS:  P00533
GTEx:  ENSG00000146648 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00533
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 12 
  • Selection Criteria: target function 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-06-09
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-05-01
    Changes: Data collection, Database references