Architecture of Eph receptor clusters Journal Article

   


Authors: Himanen, J. P.; Yermekbayeva, L.; Janes, P. W.; Walker, J. R.; Xu, K.; Atapattu, L.; Rajashankar, K. R.; Mensinga, A.; Lackmann, M.; Nikolov, D. B.; Dhe-Paganon, S.
Article Title: Architecture of Eph receptor clusters
Abstract: Eph receptor tyrosine kinases and their ephrin ligands regulate cell navigation during normal and oncogenic development. Signaling of Ephs is initiated in a multistep process leading to the assembly of higher-order signaling clusters that set off bidirectional signaling in interacting cells. However, the structural and mechanistic details of this assembly remained undefined. Herewe present high-resolution structures of the complete EphA2 ectodomain and complexes with ephrin-A1 and A5 as the base unit of an Eph cluster. The structures reveal an elongated architecture with novel Eph/Eph interactions, both within and outside of the Eph ligand-binding domain, that suggest the molecular mechanism underlying Eph/ephrin clustering. Structure-function analysis, by using site-directed mutagenesis and cell-based signaling assays, confirms the importance of the identified oligomerization interfaces for Eph clustering.
Keywords: signal transduction; protein function; cell line; protein interaction; molecular mechanics; amino acid sequence; molecular sequence data; recombinant proteins; models, molecular; crystallography, x-ray; protein structure, tertiary; multiprotein complexes; binding sites; ephrin receptor a2; protein structure; site directed mutagenesis; ligand binding; protein structure, secondary; ephrin receptor a1; oligomerization; ephrin-a1; ephrin receptor a5; cell-cell attraction and repulsion; eph receptor clustering; ephrin-a5; receptor, epha1; receptor, epha2
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 107
Issue: 24
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2010-06-15
Start Page: 10860
End Page: 10865
Language: English
DOI: 10.1073/pnas.1004148107
PUBMED: 20505120
PROVIDER: scopus
PMCID: PMC2890748
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-77954627688&partnerID=40&md5=0884f9d7c1e065689b77cdb8fee9b3de
Notes: --- - "Cited By (since 1996): 3" - "Export Date: 20 April 2011" - "CODEN: PNASA" - "Source: Scopus"
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MSK Authors
  1. Dimitar B Nikolov
    86 Nikolov
  2. Juha P Himanen
    50 Himanen
  3. Kai Xu
    21 Xu
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