CD36
Description
The CD36 (CD36 molecule (CD36 blood group)) is a protein-coding gene located on chromosome 7.
CD36 (cluster of differentiation 36), also known as platelet glycoprotein 4, fatty acid translocase (FAT), scavenger receptor class B member 3 (SCARB3), and glycoproteins 88 (GP88), IIIb (GPIIIB), or IV (GPIV) is a protein that in humans is encoded by the CD36 gene. The CD36 antigen is an integral membrane protein found on the surface of many cell types in vertebrate animals. It imports fatty acids inside cells and is a member of the class B scavenger receptor family of cell surface proteins. CD36 binds many ligands including collagen, thrombospondin, erythrocytes parasitized with Plasmodium falciparum, oxidized low density lipoprotein, native lipoproteins, oxidized phospholipids, and long-chain fatty acids. Work in genetically modified rodents suggest a role for CD36 in fatty acid metabolism, heart disease, taste, and dietary fat processing in the intestine. It may be involved in glucose intolerance, atherosclerosis, arterial hypertension, diabetes, cardiomyopathy, Alzheimer's disease and various cancers, mostly of epithelial origin (breast, prostate, ovary, and colon) and also for hepatic carcinoma and gliomas.
== Structure ==
=== Primary === In humans, rats and mice, CD36 consists of 472 amino acids with a predicted molecular weight of approximately 53,000 Da. However, CD36 is extensively glycosylated and has an apparent molecular weight of 88,000 Da as determined by SDS polyacrylamide gel electrophoresis.
=== Tertiary === Using Kyte–Doolittle analysis, the amino acid sequence of CD36 predicts a hydrophobic region near each end of the protein large enough to span cellular membranes. Based on this notion and the observation that CD36 is found on the surface of cells, CD36 is thought to have a 'hairpin-like' structure with α-helices at the C- and N- termini projecting through the membrane and a larger extracellular loop (Fig.
CD36 is a multifunctional glycoprotein that acts as a receptor for a wide range of ligands, including proteins like thrombospondin, fibronectin, collagen, and amyloid-beta, as well as lipids like oxidized low-density lipoprotein (oxLDL), anionic phospholipids, long-chain fatty acids, and bacterial diacylated lipopeptides. These ligands can bind to multiple receptors simultaneously, leading to the formation of CD36 clusters that initiate signal transduction and internalization of the receptor-ligand complexes. The specific coreceptors involved in signaling vary depending on the ligand. CD36 plays a role in various cellular processes, including angiogenesis, inflammatory response, fatty acid metabolism, taste, and dietary fat processing in the intestine. It binds long-chain fatty acids and facilitates their transport into cells, contributing to muscle lipid utilization, adipose energy storage, and gut fat absorption. Mechanistically, fatty acid binding activates the downstream kinase LYN, which phosphorylates and inactivates the palmitoyltransferase ZDHHC5, leading to CD36 depalmitoylation and caveolar endocytosis. In the small intestine, CD36 participates in the proximal absorption of dietary fatty acids and cholesterol, likely through activation of the MAPK1/3 (ERK1/2) signaling pathway. CD36 is involved in oral fat perception and preferences, leading to an increase in intracellular calcium levels in taste receptor cells and activation of gustatory neurons in the nucleus of the solitary tract. It is also an important factor in the ventromedial hypothalamus's neuronal sensing of long-chain fatty acids and the regulation of energy and glucose homeostasis. CD36 serves as a receptor for thrombospondins THBS1 and THBS2, mediating their antiangiogenic effects. It is involved in inducing apoptosis in podocytes in response to elevated free fatty acids, working together with THBS1. As a coreceptor for the TLR4:TLR6 heterodimer, CD36 promotes inflammation in monocytes and macrophages. Upon ligand binding, such as oxLDL or amyloid-beta 42, it interacts with the TLR4:TLR6 heterodimer, triggering an inflammatory response that leads to the production of various cytokines, including CXCL1, CXCL2, CCL9, CCL5, and IL1B, through different signaling pathways. CD36 acts as a selective and nonredundant sensor of microbial diacylated lipopeptides that signal via the TLR2:TLR6 heterodimer, triggering signaling from the cell surface and leading to the production of TNF via the MYD88 signaling pathway. CD36 directly mediates the cytoadherence of Plasmodium falciparum parasitized erythrocytes and the internalization of particles independently of TLR signaling. It interacts with THBS1 and THBS2, mediating their antiangiogenic activity. Upon ligand binding, such as oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42, CD36 rapidly forms a complex with TLR4 and TLR6, triggering an inflammatory signal. Through its C-terminus, CD36 interacts with PTK2, PXN, and LYN but not with SRC. LYN kinase activity is required for TLR4:TLR6 heterodimerization and signal initiation. CD36 interacts with the TLR2:TLR6 heterodimer upon binding ligands such as diacylated lipopeptides. It also interacts with CD9, CD81, FCER1G, ITGB2, and/or ITGB2, forming a membrane heteromeric complex essential for the internalization of CD36 and its ligands. When palmitoylated, CD36 interacts with ARF6, mediating its transport to the plasma membrane. CD36 binds to Plasmodium falciparum EMP1.
CD36 is also known as BDPLT10, CHDS7, FAT, GP3B, GP4, GPIV, PASIV, SCARB3.
