| Structural highlights
Function
[CLC5A_HUMAN] Functions as a positive regulator of osteoclastogenesis. Cell surface receptor that signals via TYROBP. Regulates inflammatory responses. Acts as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation (By similarity). Critical macrophage receptor for dengue virus serotypes 1-4. The binding of dengue virus to CLEC5A triggers signaling through the phosphylation of TYROBP, this interaction does not result in viral entry, but stimulates proinflammatory cytokine release.[1] [2]
Publication Abstract from PubMed
The human C-type lectin-like molecule CLEC5A is a critical macrophage receptor for dengue virus. Binding of dengue virus to CLEC5A triggers signaling through the associated adapter molecule DAP12, stimulating proinflammatory cytokine release. We crystallized an informative ensemble of CLEC5A structural isoforms at 1.9 Angstrom resolution, and demonstrate how an on-off extension to a beta-sheet acts as a binary switch regulating the flexibility of the molecule. This structural information together with molecular dynamics simulations, suggests a mechanism whereby extracellular events may be transmitted through the membrane and influence DAP12 signaling. We demonstrate that CLEC5A is homodimeric and binds to dengue virus serotypes 1-4. Using blotting experiments, surface analyses and docking studies, we investigate the interaction of CLEC5A with dengue virus, mannose, fucose and associated sugars and highlight three distinct potential ligand binding sites. This study provides a rational foundation for understanding the dengue virus-macrophage interaction and the role of CLEC5A in dengue virus-induced lethal disease.
Structural flexibility of the macrophage dengue virus receptor CLEC5A: Implications for ligand binding and signaling.,Watson AA, Lebedev AA, Hall BA, Fenton-May AE, Vagin AA, Dejnirattisai W, Felce J, Mongkolsapaya J, Palma AS, Liu Y, Feizi T, Screaton GR, Murshudov GN, O'Callaghan CA J Biol Chem. 2011 May 12. PMID:21566123[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bakker AB, Baker E, Sutherland GR, Phillips JH, Lanier LL. Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells. Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9792-6. PMID:10449773
- ↑ Chen ST, Lin YL, Huang MT, Wu MF, Cheng SC, Lei HY, Lee CK, Chiou TW, Wong CH, Hsieh SL. CLEC5A is critical for dengue-virus-induced lethal disease. Nature. 2008 May 29;453(7195):672-6. doi: 10.1038/nature07013. Epub 2008 May 21. PMID:18496526 doi:http://dx.doi.org/10.1038/nature07013
- ↑ Watson AA, Lebedev AA, Hall BA, Fenton-May AE, Vagin AA, Dejnirattisai W, Felce J, Mongkolsapaya J, Palma AS, Liu Y, Feizi T, Screaton GR, Murshudov GN, O'Callaghan CA. Structural flexibility of the macrophage dengue virus receptor CLEC5A: Implications for ligand binding and signaling. J Biol Chem. 2011 May 12. PMID:21566123 doi:10.1074/jbc.M111.226142
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