| Structural highlights
5lgd is a 2 chain structure with sequence from Human and Plafa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , |
| Gene: | CD36, GP3B, GP4 (HUMAN), MCvar-1 PfEMP1 (PLAFA) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[CD36_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Patients also have postprandial hypertriglyceridemia, insulin resistance and hypertension increasing atherosclerotic risk.[1] Disease susceptibility is associated with variations affecting the gene represented in this entry.
Function
[CD36_HUMAN] Multifunctional glycoprotein that acts as receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipidic nature such as oxidized low-density lipoprotein (oxLDL), anionic phospholipids, long-chain fatty acids and bacterial diacylated lipopeptides. They are generally multivalent and can therefore engage multiple receptors simultaneously, the resulting formation of CD36 clusters initiates signal transduction and internalization of receptor-ligand complexes. The dependency on coreceptor signaling is strongly ligand specific. Cellular responses to these ligands are involved in angiogenesis, inflammatory response, fatty acid metabolism, taste and dietary fat processing in the intestine (Probable). Binds long-chain fatty acids and facilitates their transport into cells, thus participating in muscle lipid utilization, adipose energy storage, and gut fat absorption (By similarity) (PubMed:18353783, PubMed:21610069). In the small intestine, plays a role in proximal absorption of dietary fatty acid and cholesterol for optimal chylomicron formation, possibly through the activation of MAPK1/3 (ERK1/2) signaling pathway (By similarity) (PubMed:18753675). Involved in oral fat perception and preferences (PubMed:22240721, PubMed:25822988). Detection into the tongue of long-chain fatty acids leads to a rapid and sustained rise in flux and protein content of pancreatobiliary secretions (By similarity). In taste receptor cells, mediates the induction of an increase in intracellulare calcium levels by long-chain fatty acids, leading to the activation of the gustatory neurons in the nucleus of the solitary tract (By similarity). Important factor in both ventromedial hypothalamus neuronal sensing of long-chain fatty acid and the regulation of energy and glucose homeostasis (By similarity). Receptor for thombospondins, THBS1 and THBS2, mediating their antiangiogenic effects (By similarity). As a coreceptor for TLR4:TLR6 heterodimer, promotes inflammation in monocytes/macrophages. Upon ligand binding, such as oxLDL or amyloid-beta 42, interacts with the heterodimer TLR4:TLR6, the complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion, through the priming and activation of the NLRP3 inflammasome (By similarity) (PubMed:20037584). Selective and nonredundant sensor of microbial diacylated lipopeptide that signal via TLR2:TLR6 heterodimer, this cluster triggers signaling from the cell surface, leading to the NF-kappa-B-dependent production of TNF, via MYD88 signaling pathway and subsequently is targeted to the Golgi in a lipid-raft dependent pathway (By similarity) (PubMed:16880211).[UniProtKB:Q07969][UniProtKB:Q08857][2] [3] [4] [5] [6] [7] [8] [9] (Microbial infection) Directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes and the internalization of particles independently of TLR signaling.[10] [11] [12]
Publication Abstract from PubMed
CD36 is a scavenger receptor involved in fatty acid metabolism, innate immunity and angiogenesis. It interacts with lipoprotein particles and facilitates uptake of long chain fatty acids. It is also the most common target of the PfEMP1 proteins of the malaria parasite, Plasmodium falciparum, tethering parasite-infected erythrocytes to endothelial receptors. This prevents their destruction by splenic clearance and allows increased parasitaemia. Here we describe the structure of CD36 in complex with long chain fatty acids and a CD36-binding PfEMP1 protein domain. A conserved hydrophobic pocket allows the hugely diverse PfEMP1 protein family to bind to a conserved phenylalanine residue at the membrane distal tip of CD36. This phenylalanine is also required for CD36 to interact with lipoprotein particles. By targeting a site on CD36 that is required for its physiological function, PfEMP1 proteins maintain the ability to tether to the endothelium and avoid splenic clearance.
The structural basis for CD36 binding by the malaria parasite.,Hsieh FL, Turner L, Bolla JR, Robinson CV, Lavstsen T, Higgins MK Nat Commun. 2016 Sep 26;7:12837. doi: 10.1038/ncomms12837. PMID:27667267[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Masuda D, Hirano K, Oku H, Sandoval JC, Kawase R, Yuasa-Kawase M, Yamashita Y, Takada M, Tsubakio-Yamamoto K, Tochino Y, Koseki M, Matsuura F, Nishida M, Kawamoto T, Ishigami M, Hori M, Shimomura I, Yamashita S. Chylomicron remnants are increased in the postprandial state in CD36 deficiency. J Lipid Res. 2009 May;50(5):999-1011. doi: 10.1194/jlr.P700032-JLR200. Epub 2008 , Aug 27. PMID:18753675 doi:http://dx.doi.org/10.1194/jlr.P700032-JLR200
- ↑ Triantafilou M, Gamper FG, Haston RM, Mouratis MA, Morath S, Hartung T, Triantafilou K. Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. J Biol Chem. 2006 Oct 13;281(41):31002-11. Epub 2006 Jul 31. PMID:16880211 doi:http://dx.doi.org/10.1074/jbc.M602794200
- ↑ Smith J, Su X, El-Maghrabi R, Stahl PD, Abumrad NA. Opposite regulation of CD36 ubiquitination by fatty acids and insulin: effects on fatty acid uptake. J Biol Chem. 2008 May 16;283(20):13578-85. doi: 10.1074/jbc.M800008200. Epub 2008, Mar 18. PMID:18353783 doi:http://dx.doi.org/10.1074/jbc.M800008200
- ↑ Masuda D, Hirano K, Oku H, Sandoval JC, Kawase R, Yuasa-Kawase M, Yamashita Y, Takada M, Tsubakio-Yamamoto K, Tochino Y, Koseki M, Matsuura F, Nishida M, Kawamoto T, Ishigami M, Hori M, Shimomura I, Yamashita S. Chylomicron remnants are increased in the postprandial state in CD36 deficiency. J Lipid Res. 2009 May;50(5):999-1011. doi: 10.1194/jlr.P700032-JLR200. Epub 2008 , Aug 27. PMID:18753675 doi:http://dx.doi.org/10.1194/jlr.P700032-JLR200
- ↑ Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, Lacy-Hulbert A, El Khoury J, Golenbock DT, Moore KJ. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. 2010 Feb;11(2):155-61. doi: 10.1038/ni.1836. Epub 2009 Dec 27. PMID:20037584 doi:http://dx.doi.org/10.1038/ni.1836
- ↑ Tran TT, Poirier H, Clement L, Nassir F, Pelsers MM, Petit V, Degrace P, Monnot MC, Glatz JF, Abumrad NA, Besnard P, Niot I. Luminal lipid regulates CD36 levels and downstream signaling to stimulate chylomicron synthesis. J Biol Chem. 2011 Jul 15;286(28):25201-10. doi: 10.1074/jbc.M111.233551. Epub, 2011 May 24. PMID:21610069 doi:http://dx.doi.org/10.1074/jbc.M111.233551
- ↑ Keller KL, Liang LC, Sakimura J, May D, van Belle C, Breen C, Driggin E, Tepper BJ, Lanzano PC, Deng L, Chung WK. Common variants in the CD36 gene are associated with oral fat perception, fat preferences, and obesity in African Americans. Obesity (Silver Spring). 2012 May;20(5):1066-73. doi: 10.1038/oby.2011.374. Epub , 2012 Jan 12. PMID:22240721 doi:http://dx.doi.org/10.1038/oby.2011.374
- ↑ Mrizak I, Sery O, Plesnik J, Arfa A, Fekih M, Bouslema A, Zaouali M, Tabka Z, Khan NA. The A allele of cluster of differentiation 36 (CD36) SNP 1761667 associates with decreased lipid taste perception in obese Tunisian women. Br J Nutr. 2015 Apr 28;113(8):1330-7. doi: 10.1017/S0007114515000343. Epub 2015, Mar 30. PMID:25822988 doi:http://dx.doi.org/10.1017/S0007114515000343
- ↑ Silverstein RL, Febbraio M. CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, and behavior. Sci Signal. 2009 May 26;2(72):re3. doi: 10.1126/scisignal.272re3. PMID:19471024 doi:http://dx.doi.org/10.1126/scisignal.272re3
- ↑ Aitman TJ, Cooper LD, Norsworthy PJ, Wahid FN, Gray JK, Curtis BR, McKeigue PM, Kwiatkowski D, Greenwood BM, Snow RW, Hill AV, Scott J. Malaria susceptibility and CD36 mutation. Nature. 2000 Jun 29;405(6790):1015-6. PMID:10890433 doi:http://dx.doi.org/10.1038/35016636
- ↑ Omi K, Ohashi J, Patarapotikul J, Hananantachai H, Naka I, Looareesuwan S, Tokunaga K. CD36 polymorphism is associated with protection from cerebral malaria. Am J Hum Genet. 2003 Feb;72(2):364-74. Epub 2002 Dec 27. PMID:12506336 doi:http://dx.doi.org/S0002-9297(07)60545-X
- ↑ Erdman LK, Cosio G, Helmers AJ, Gowda DC, Grinstein S, Kain KC. CD36 and TLR interactions in inflammation and phagocytosis: implications for malaria. J Immunol. 2009 Nov 15;183(10):6452-9. doi: 10.4049/jimmunol.0901374. Epub 2009, Oct 28. PMID:19864601 doi:http://dx.doi.org/10.4049/jimmunol.0901374
- ↑ Hsieh FL, Turner L, Bolla JR, Robinson CV, Lavstsen T, Higgins MK. The structural basis for CD36 binding by the malaria parasite. Nat Commun. 2016 Sep 26;7:12837. doi: 10.1038/ncomms12837. PMID:27667267 doi:http://dx.doi.org/10.1038/ncomms12837
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