Receptor ephrin

Ephrin receptor B2 (EphB2) Inactive insert, and C-terminal tail Juxtamembrane and N-terminal lobe inhibited by... 

Ephrins are a group of membranous ligands, which function through a family of receptor tyrosine kinases (Ephs). Ephrin/Eph-mediated signaling processes are involved in morphogenetic processes taking place e.g. during the development of the nervous system or the vasculature. 

Fig. 1. Schematic representation of the domain organization of Eph receptors and ephrins. SAM, sterile alpha motif.

Fig. 2. Structures of the extracellular domains of Ephs and ephrins. The molecular surfaces (semi-transparent) are also indicated. (A) Structure of the ligand-binding domain of EphB2. The N- and C-termini of the molecule are labeled, as are the class-specificity loop (H-I) and the ligand-binding loops that are largely disordered in the absence of bound ephrin. (B) Structure of the extracellular receptor-binding domain of ephrin-B2. Indicated is the location of the receptor-binding G-H loop. (C) Structure of the EphB2/ephrin-B2 tetramer. Eph receptors are blue and ephrins are green. The high-affinity dimerization interfaces are indicated by arrows. (See Color Insert.)...

The ephrins possess a unique N-terminal receptor-binding domain (RBD) (Fig. 1), which is separated from the membrane via a linker of approximately forty amino acids. A-ephrins are attached to the cell via a GPl linkage. B-type ephrins have a transmembrane region and short but conserved 80-amino-acid cytoplasmic domain, which harbors a C-terminal PDZ-binding motif. 

Himanen et al, 2001 Toth et at, 2001). In the crystals of uncomplexed ephrin-B2, the molecule forms homodimers by burying the hydrophobic surface regions around the G H loop. Since this same loop is involved in receptor binding, the ephrin molecules might exhibit significant rearrangement when their homodimers are displaced upon interaction with the Eph receptors. 

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