Title : Crystal structure of the human
ephrin-A5 ectodomain
Abstract :
- The Eph receptors , the largest subfamily of receptor tyrosine kinases, and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, pathfinding, and mobility in the nervous and cardiovascular systems
- Recent structural studies have revealed unique molecular features that explain many of the biochemical and signaling properties of Ephs and ephrins
- Nevertheless, open questions remain, including understanding the precise molecular mechanism underlining their binding-partner preferences and subclass specificity
- In this study, we have determined and present the crystal structure of the extracellular domain of ephrin-A5-the first structure of an unbound A-class ephrin
- The structure, determined at 2.1 A resolution, is a variation of the Greek key beta-barrel folding topology, containing eight beta-strands, and stabilized by two disulphide bonds
- Overall, ephrin-A5 is structurally very similar to ephrin-B1 and ephrin-B2 but, unlike ephrin-B2 , it does not show dimerization either in solution or in the crystals
- Comparing free ephrin-A5 to the previously published structure of EphB2-bound ephrin-A5 reveals that significant conformational changes occur only around the G-H ephrin loop that upon binding bends toward the receptor
- Interestingly, the G-H loop undergoes a very similar conformational rearrangement in ephrin-B2 upon receptor binding
- The results of this study further emphasize the importance of the G-H loop for receptor recognition and selectivity, and could serve as a starting point for the development of structure-based Eph antagonists