3HPN

Ligand recognition by A-class EPH receptors: crystal structures of the EPHA2 ligand-binding domain and the EPHA2/EPHRIN-A1 complex

Summary for 3HPN

• Entry DOI: 10.2210/pdb3hpn/pdb
• Descriptor: Ephrin type-A receptor 2 (2 entities in total)
• Functional Keywords: eph receptor tyrosine kinase, ephrin, atp-binding, glycoprotein, kinase, membrane, nucleotide-binding, phosphoprotein, receptor, transferase, transmembrane, tyrosine-protein kinase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein: P29317
• Total number of polymer chains: 6
• Total formula weight: 119481.55

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: 2009-06-04, release date: 2009-06-30, Last modification date: 2024-11-20)

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 (2.52 Å)