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. Here we 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Himanen JP,Yermekbayeva L,Janes PW,Walker JR,Xu K,Atapattu L,Rajashankar KR,Mensinga A,Lackmann M,Nikolov DB,Dhe-Paganon Sdoi
10.1073/pnas.1004148107subject
Has Abstractpub_date
2010-06-15 00:00:00pages
10860-5issue
24eissn
0027-8424issn
1091-6490pii
1004148107journal_volume
107pub_type
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