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. 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.

authors

Himanen JP,Yermekbayeva L,Janes PW,Walker JR,Xu K,Atapattu L,Rajashankar KR,Mensinga A,Lackmann M,Nikolov DB,Dhe-Paganon S

doi

10.1073/pnas.1004148107

subject

Has Abstract

pub_date

2010-06-15 00:00:00

pages

10860-5

issue

24

eissn

0027-8424

issn

1091-6490

pii

1004148107

journal_volume

107

pub_type

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