Eph Receptors and Ephrins

Expression Profiles and Biological Roles of Ephs and Ephrins 

Analysis of Eph and ephrin protein expression has been carried out in several species including zebrafish, Xenopus, mouse, rat, and chicken embryos (reviewed in Boyd and Lackmann, 2001). They are broadly 

Ligand-binding Cysteine-rich Fibronectin III (FN HI) Fibronectin III 

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. 

X-ray crystallographic studies revealed that the ephrin RBD has a globular /3-barrel structure (Fig. 2B) with a Greek key folding topology 

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

Dodelet, V. C., and Pasquale, E. B. (2000). Eph receptors and ephrin ligands Embryo-genesis to tumorigenesis. Oncogene 19, 5614—5619. 

Mellitzer, G., Xu, Q., Wilkinson, D. 1999. Eph receptors and ephrins restrict cell intermingling and communication. Nature 400, 77-81. 

Wilkinson, D.G. 2001. Multiple roles of EPH receptors and ephrins in neural development. Nat. Rev. Neurosci. 2, 155-164. 

Torres, R. et al. (1998). PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands. Neuron 21, 1453-1463. 

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.)...

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