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PROSITE documentation PDOC51550Eph receptor ligand binding (Eph LBD) domain profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC51550
The Eph receptors, which bind a group of cell-membrane-anchored ligands known as ephrins, represent the largest subfamily of receptor tyrosine kinases (RTKs) (see <PDOC00629>). The Eph receptors and their ephrin ligands control a diverse array of cell-cell interactions in the nervous and vascular systems. On ephrin binding, the Eph kinase domain is activated, initiating 'forward' signaling in the receptor-expressing cells. Simultaneously, signals are also induced in the ligand-expressing cells a phenomenon referred to as 'reverse' signalling. The extracellular Eph receptor region contains a conserved 180-amino-acid N-terminal ligand-binding domain (LBD) which is both necessary and sufficient for bindings of the receptors to their ephrin ligands. An adjacent cysteine-rich region might be involved in receptor-receptor oligomerization often observed on ligand binding, whereas the next two fibronectin type III repeats (see <PDOC50853>) have yet to be assigned a clear biological function. The cytoplasmic Eph receptor region contains a kinase domain (see <PDOC00100>), a sterile α motif (SAM) domain (see <PDOC50105>), and a PDZ-binding motif. The ligand-binding domain (LBD) of Eph receptors is unique to this family of RTKs ans shares no significant amino-acid-sequence homology with other known proteins [1,2,3].
The Eph LBD domain forms a compact globular structure which folds into a jellyroll β-sandwich composed of 11 antiparallel β-strands (see <PDB:1NUK>). It has two antiparallel β-sheets, with the usual left-handed twist, packed against each other to form a compact β-sandwich, and a short 3(10) helix [1,2,3].
The profile we developed covers the entire Eph LBD domain.
Last update:October 2011 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Himanen J.-P. Henkemeyer M. Nikolov D.B. |
| Title | Crystal structure of the ligand-binding domain of the receptor tyrosine kinase EphB2. | |
| Source | Nature 396:486-491(1998). | |
| PubMed ID | 9853759 | |
| DOI | 10.1038/24904 |
| 2 | Authors | Himanen J.-P. Rajashankar K.R. Lackmann M. Cowan C.A. Henkemeyer M. Nikolov D.B. |
| Title | Crystal structure of an Eph receptor-ephrin complex. | |
| Source | Nature 414:933-938(2001). | |
| PubMed ID | 11780069 | |
| DOI | 10.1038/414933a |
| 3 | Authors | Himanen J.-P. Goldgur Y. Miao H. Myshkin E. Guo H. Buck M. Nguyen M. Rajashankar K.R. Wang B. Nikolov D.B. |
| Title | Ligand recognition by A-class Eph receptors: crystal structures of the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex. | |
| Source | EMBO Rep. 10:722-728(2009). | |
| PubMed ID | 19525919 | |
| DOI | 10.1038/embor.2009.91 |
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