2X10

Crystal structure of the complete EphA2 ectodomain

Summary for 2X10

• Entry DOI: 10.2210/pdb2x10/pdb
• Related: 1MQB 2X11
• Descriptor: EPHRIN TYPE-A RECEPTOR 2, CHLORIDE ION, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: transferase, angiogenesis, kinase, cataract, receptor, apoptosis, glycoprotein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 60678.61

Authors

Seiradake, E.,Harlos, K.,Sutton, G.,Aricescu, A.R.,Jones, E.Y. (deposition date: 2009-12-21, release date: 2010-03-16, Last modification date: 2024-11-06)

Primary citation

Seiradake, E.,Harlos, K.,Sutton, G.,Aricescu, A.R.,Jones, E.Y.
An Extracellular Steric Seeding Mechanism for Eph-Ephrin Signalling Platform Assembly
Nat.Struct.Mol.Biol., 17:398-, 2010

PubMed 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.

PubMed: 20228801
DOI: 10.1038/NSMB.1782

Experimental method

X-RAY DIFFRACTION (3 Å)