3HEI

Ligand Recognition by A-Class Eph Receptors: Crystal Structures of the EphA2 Ligand-Binding Domain and the EphA2/ephrin-A1 Complex

Summary for 3HEI

• Entry DOI: 10.2210/pdb3hei/pdb
• Descriptor: Ephrin type-A receptor 2, Ephrin-A1 (3 entities in total)
• Functional Keywords: eph receptor tyrosine kinase, ephrin, cell membrane, disulfide bond, glycoprotein, gpi-anchor, lipoprotein, membrane, atp-binding, kinase, nucleotide-binding, phosphoprotein, receptor, transferase, transmembrane, tyrosine-protein kinase, transferase-signaling protein complex, transferase/signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane ; Single-pass type I membrane protein : P29317; Cell membrane ; Lipid-anchor, GPI-anchor . Ephrin-A1, secreted form: Secreted : P20827
• Total number of polymer chains: 16
• Total formula weight: 286387.29

Authors

Himanen, J.P.,Goldgur, Y.,Miao, H.,Myshkin, E.,Guo, H.,Buck, M.,Nguyen, M.,Rajashankar, K.R.,Wang, B.,Nikolov, D.B. (deposition date: 2009-05-08, release date: 2009-06-30, Last modification date: 2021-03-31)

Primary citation

Himanen, J.P.,Goldgur, Y.,Miao, H.,Myshkin, E.,Guo, H.,Buck, M.,Nguyen, M.,Rajashankar, K.R.,Wang, B.,Nikolov, D.B.
Ligand recognition by A-class Eph receptors: crystal structures of the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex.
Embo Rep., 10:722-728, 2009

PubMed Abstract: Ephrin (Eph) receptor tyrosine kinases fall into two subclasses (A and B) according to preferences for their ephrin ligands. All published structural studies of Eph receptor/ephrin complexes involve B-class receptors. Here, we present the crystal structures of an A-class complex between EphA2 and ephrin-A1 and of unbound EphA2. Although these structures are similar overall to their B-class counterparts, they reveal important differences that define subclass specificity. The structures suggest that the A-class Eph receptor/ephrin interactions involve smaller rearrangements in the interacting partners, better described by a 'lock-and-key'-type binding mechanism, in contrast to the 'induced fit' mechanism defining the B-class molecules. This model is supported by structure-based mutagenesis and by differential requirements for ligand oligomerization by the two subclasses in cell-based Eph receptor activation assays. Finally, the structure of the unligated receptor reveals a homodimer assembly that might represent EphA2-specific homotypic cell adhesion interactions.

PubMed: 19525919
DOI: 10.1038/embor.2009.91

Experimental method

X-RAY DIFFRACTION (2 Å)