Eph receptors

Drescher, U., Kremoser, C., Handwerker, C. et al. In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases. Cell 82 359-370,1995. 

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.)...

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. 

Fig. 5. Structures of the intracellular domains of Eph receptors. (A) Structure of the EphB2 kinase domain autoinhibited by the nonphosphorylated juxtamembrane region. The C-terminal kinase lobe is green and the N-terminal lobe is brown. The two regulatory tyrosine residues in the blue juxtamembrane region are shown in red. The ATP location in the active site is indicated in gray. (B) Structure of the monomeric sterile a motif (SAM) domain of EpliA4. Reproduced with permission from (Himanen et al, 2003b). (See Color Insert.)...

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

Gale, N. W. et al. (1996). Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron 17, 9-19. 

Himanen, J.-P. et al. (2001). Crystal structure of an Eph receptor-ephrin complex. Nature 414, 933-938. 

Stapleton, D. et al. (1999). The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization. Nature Struct. Biol. 6, 44—49. 

Stein, E. et al. (1998). Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses. Genes Dev. 12, 667-678. 

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

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