PDBsum entry 2x10

Receptor

PDB id: 2x10

Contents

Protein chain

485 a.a.

Ligands

NAG

Metals

_CL

References listed in PDB file

Key reference

• Title: An extracellular steric seeding mechanism for eph-Ephrin signaling platform assembly.
• Authors: E.Seiradake, K.Harlos, G.Sutton, A.R.Aricescu, E.Y.Jones.
• Ref.: Nat Struct Biol, 2010, 17, 398-402.
• PubMed id: 20228801

Abstract

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.