Architecture of Eph receptor clusters Academic Article uri icon

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

publication date

  • June 15, 2010