Structure of the ligand-binding domain of the EphB2 receptor at 2 Å resolution Journal Article


Authors: Goldgur, Y.; Paavilainen, S.; Nikolov, D.; Himanen, J. P.
Article Title: Structure of the ligand-binding domain of the EphB2 receptor at 2 Å resolution
Abstract: Eph tyrosine kinase receptors, the largest group of receptor tyrosine kinases, and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape and mobility. Recently, several Eph receptors and ephrins have also been found to play important roles in the progression of cancer. Structural and biophysical studies have established detailed information on the binding and recognition of Eph receptors and ephrins. The initial high-affinity binding of Eph receptors to ephrin occurs through the penetration of an extended G-H loop of the ligand into a hydrophobic channel on the surface of the receptor. Consequently, the G-H loop-binding channel of Eph receptors is the main target in the search for Eph antagonists that could be used in the development of anticancer drugs and several peptides have been shown to specifically bind Eph receptors and compete with the cognate ephrin ligands. However, the molecular details of the conformational changes upon Eph/ephrin binding have remained speculative, since two of the loops were unstructured in the original model of the free EphB2 structure and their conformational changes upon ligand binding could consequently not be analyzed in detail. In this study, the X-ray structure of unbound EphB2 is reported at a considerably higher 2 Å resolution, the conformational changes that the important receptor loops undergo upon ligand binding are described and the consequences that these findings have for the development of Eph antagonists are discussed. © International Union of Crystallography 2009.
Keywords: comparative study; mouse; animal; metabolism; animals; mice; classification; protein binding; physiology; chemistry; ligand; ligands; crystallography, x-ray; protein structure, tertiary; protein secondary structure; x ray crystallography; eph receptors; ephb2; ligand binding; ephrin receptor b2; protein tertiary structure; protein structure, secondary; receptor, ephb2
Journal Title: Acta Crystallographica Section F: Structural Biology Communications
Volume: 65
Issue: 2
ISSN: 2053-230X
Publisher: Wiley Blackwell  
Date Published: 2009-02-01
Start Page: 71
End Page: 74
Language: English
DOI: 10.1107/s1744309108043078
PUBMED: 19193989
PROVIDER: scopus
PMCID: PMC2635866
DOI/URL:
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 30 November 2010" - "Source: Scopus"
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MSK Authors
  1. Dimitar B Nikolov
    86 Nikolov
  2. Juha P Himanen
    50 Himanen
  3. Yehuda Goldgur
    42 Goldgur