Structural highlights
Function
[GLYCP_NIPAV] Interacts with host ephrinB2/EFNB2 or ephrin B3/EFNB3 to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis.[1] [2] [EFNB2_HUMAN] Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds to receptor tyrosine kinase including EPHA4, EPHA3 and EPHB4. Together with EPHB4 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. May play a role in constraining the orientation of longitudinally projecting axons.[3]
Evolutionary Conservation
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Publication Abstract from PubMed
Nipah and Hendra viruses are emergent paramyxoviruses, causing disease characterized by rapid onset and high mortality rates, resulting in their classification as Biosafety Level 4 pathogens. Their attachment glycoproteins are essential for the recognition of the cell-surface receptors ephrin-B2 (EFNB2) and ephrin-B3 (EFNB3). Here we report crystal structures of both Nipah and Hendra attachment glycoproteins in complex with human EFNB2. In contrast to previously solved paramyxovirus attachment complexes, which are mediated by sialic acid interactions, the Nipah and Hendra complexes are maintained by an extensive protein-protein interface, including a crucial phenylalanine side chain on EFNB2 that fits snugly into a hydrophobic pocket on the viral protein. By analogy with the development of antivirals against sialic acid binding viruses, these results provide a structural template to target antiviral inhibition of protein-protein interactions.
Structural basis of Nipah and Hendra virus attachment to their cell-surface receptor ephrin-B2.,Bowden TA, Aricescu AR, Gilbert RJ, Grimes JM, Jones EY, Stuart DI Nat Struct Mol Biol. 2008 Jun;15(6):567-72. Epub 2008 May 18. PMID:18488039[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Diederich S, Maisner A. Molecular characteristics of the Nipah virus glycoproteins. Ann N Y Acad Sci. 2007 Apr;1102:39-50. PMID:17470910 doi:http://dx.doi.org/10.1196/annals.1408.003
- ↑ Diederich S, Moll M, Klenk HD, Maisner A. The nipah virus fusion protein is cleaved within the endosomal compartment. J Biol Chem. 2005 Aug 19;280(33):29899-903. Epub 2005 Jun 16. PMID:15961384 doi:http://dx.doi.org/10.1074/jbc.M504598200
- ↑ Fuller T, Korff T, Kilian A, Dandekar G, Augustin HG. Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells. J Cell Sci. 2003 Jun 15;116(Pt 12):2461-70. Epub 2003 May 6. PMID:12734395 doi:10.1242/jcs.00426
- ↑ Bowden TA, Aricescu AR, Gilbert RJ, Grimes JM, Jones EY, Stuart DI. Structural basis of Nipah and Hendra virus attachment to their cell-surface receptor ephrin-B2. Nat Struct Mol Biol. 2008 Jun;15(6):567-72. Epub 2008 May 18. PMID:18488039 doi:10.1038/nsmb.1435
