2x11

Publication Abstract from PubMed

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays.

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly.,Seiradake E, Harlos K, Sutton G, Aricescu AR, Jones EY Nat Struct Mol Biol. 2010 Apr;17(4):398-402. Epub 2010 Mar 14. PMID:20228801^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.