Architecture of Eph receptor clusters

Journal Article · Mon Oct 04 04:00:00 EDT 2010 · Proc. Natl. Acad. Sci. USA

DOI:https://doi.org/10.1073/pnas.1004148107· OSTI ID:1002479

Himanen, Juha P; Yermekbayeva, Laila; Janes, Peter W; Walker, John R; Xu, Kai; Atapattu, Lakmali; Rajashankar, Kanagalaghatta R; Mensinga, Anneloes; Lackmann, Martin; Nikolov, Dimitar B; Dhe-Paganon, Sirano ^[1]

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1. Cornell

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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002479
• Journal Information: Proc. Natl. Acad. Sci. USA, Journal Name: Proc. Natl. Acad. Sci. USA Journal Issue: (24) ; 06, 2010 Vol. 107; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
ARCHITECTURE
MUTAGENESIS
NAVIGATION
PHOSPHOTRANSFERASES
TYROSINE