Crystal structure of the ephrin-B1 ectodomain: Implications for receptor recognition and signaling Journal Article
| Authors: | Nikolov, D. B.; Li, C.; Barton, W. A.; Himanen, J. P. |
| Article Title: | Crystal structure of the ephrin-B1 ectodomain: Implications for receptor recognition and signaling |
| Abstract: | Eph receptors and their ephrin ligands are involved in various aspects of cell-cell communication during development, including axonal pathfinding in the nervous system and cell-cell interactions of the vascular endothelial cells. Recent structural studies revealed unique molecular features, not previously seen in any other receptor-ligand families, and explained many of the biochemical and signaling properties of Ephs and ephrins. However, unresolved questions remain regarding the potential oligomerization and clustering of these important signaling molecules. In this study, the biophysical properties and receptor-binding preferences of the extracellular domain of ephrin-B1 were investigated and its crystal structure was determined at 2.65 Å resolution. Ephrin-B1 is a monomer both in solution and in the crystals, while it was previously shown that the closely related ephrin-B2 forms homodimers. The main structural difference between ephrin-B1 and ephrin-B2 is the conformation of the receptor-binding G-H loop and the partially disordered N-terminal tetramerization region of ephrin-B1. The G-H loop is structurally rigid in ephrin-B2 and adopts the same conformation in both the receptor-bound and unbound ligand, where it mediates receptor-independent homodimerization. In the ephrin-B1 structure, on the other hand, the G-H loop is not involved in any homotypic interactions and adopts a new, distinct conformation. The implications of the ephrin-B1 structure, in context of available ephrin-B1 mutagenesis data, for the mechanism of Eph-ephrin recognition and signaling initiation are discussed. © 2005 American Chemical Society. |
| Keywords: | signal transduction; human cell; protein conformation; protein domain; animals; mice; endothelial cells; amino acid sequence; molecular sequence data; amino terminal sequence; vascular endothelium; molecular recognition; nerve fiber; ligand; ligands; crystal structure; dimerization; crystallography, x-ray; protein structure, tertiary; structure analysis; biochemistry; cell interaction; cell communication; protein structure, secondary; mutagenesis; axons; oligomerization; receptor binding; monomer; neurology; ephrin ligands; ephrin b2; oligomers; homodimers; ephrin receptor; dimers; ephrin b1; ephrin-b2; data acquisition; ephrin-b1 ectodomain; receptor-independent homodimerization; ephrin-b1 |
| Journal Title: | Biochemistry |
| Volume: | 44 |
| Issue: | 33 |
| ISSN: | 0006-2960 |
| Publisher: | American Chemical Society |
| Date Published: | 2005-08-23 |
| Start Page: | 10947 |
| End Page: | 10953 |
| Language: | English |
| DOI: | 10.1021/bi050789w |
| PUBMED: | 16101278 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 18" - "Export Date: 24 October 2012" - "CODEN: BICHA" - "Source: Scopus" |
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