Crystal structure of the human ephrin-A5 ectodomain Journal Article
| Authors: | Nikolov, D.; Li, C.; Lackmann, M.; Jeffrey, P.; Himanen, J. |
| Article 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 Å resolution, is a variation of the Greek key β-barrel folding topology, containing eight β-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. Published by Cold Spring Harbor Laboratory Press. Copyright © 2007 The Protein Society. |
| Keywords: | controlled study; protein expression; human cell; protein conformation; protein domain; protein binding; protein interaction; enzyme activity; tyrosine kinase receptor; crystal structure; models, molecular; dimerization; crystallography, x-ray; protein structure, tertiary; receptor protein-tyrosine kinases; conformational transition; protein folding; protein structure; crystallization; receptor binding; x-ray crystallography; ephrin b2; ephrin-a5; ephrin receptor; ligand-receptor recognition; receptor tyrosine kinase signaling; ephrin a5; ephrin b1 |
| Journal Title: | Protein Science |
| Volume: | 16 |
| Issue: | 5 |
| ISSN: | 0961-8368 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2007-05-01 |
| Start Page: | 996 |
| End Page: | 1000 |
| Language: | English |
| DOI: | 10.1110/ps.062665807 |
| PUBMED: | 17400922 |
| PROVIDER: | scopus |
| PMCID: | PMC2206647 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 17 November 2011" - "CODEN: PRCIE" - "Source: Scopus" |
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