Editing CD36 (section)

== Structure ==

=== Primary ===

In [https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_000063.2 humans], [https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_113749.2 rats] and [https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_031669.2 mice], CD36 consists of 472 amino acids with a predicted molecular weight of approximately 53,000 [[Atomic mass unit|Da]]. However, CD36 is extensively glycosylated and has an apparent molecular weight of 88,000 [[Atomic mass unit|Da]] as determined by [[SDS-PAGE|SDS polyacrylamide gel electrophoresis]].<ref name="pmid1699598">{{cite journal | vauthors = Greenwalt DE, Watt KW, So OY, Jiwani N | title = PAS IV, an integral membrane protein of mammary epithelial cells, is related to platelet and endothelial cell CD36 (GP IV) | journal = Biochemistry | volume = 29 | issue = 30 | pages = 7054–9 | date = July 1990 | pmid = 1699598 | doi = 10.1021/bi00482a015 }}</ref>

=== Tertiary ===

Using [[Hydrophobicity scales|Kyte–Doolittle analysis]],<ref name="pmid7108955">{{cite journal | vauthors = Kyte J, Doolittle RF | title = A simple method for displaying the hydropathic character of a protein | journal = Journal of Molecular Biology | volume = 157 | issue = 1 | pages = 105–32 | date = May 1982 | pmid = 7108955 | doi = 10.1016/0022-2836(82)90515-0 | citeseerx = 10.1.1.458.454 }}</ref> the [[peptide sequence|amino acid sequence]] of CD36 predicts a [[hydrophobic]] region near each end of the protein large enough to span [[cell membrane|cellular membrane]]s. 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 [[alpha helix|α-helices]] at the C- and N- termini projecting through the [[cell membrane|membrane]] and a larger extracellular loop (Fig. 1). This [[membrane topology|topology]] is supported by transfection experiments in cultured cells using deletion mutants of CD36.<ref name="pmid10964685">{{cite journal | vauthors = Gruarin P, Thorne RF, Dorahy DJ, Burns GF, Sitia R, Alessio M | title = CD36 is a ditopic glycoprotein with the N-terminal domain implicated in intracellular transport | journal = Biochemical and Biophysical Research Communications | volume = 275 | issue = 2 | pages = 446–54 | date = August 2000 | pmid = 10964685 | doi = 10.1006/bbrc.2000.3333 }}</ref><ref name="pmid8798390">{{cite journal | vauthors = Tao N, Wagner SJ, Lublin DM | title = CD36 is palmitoylated on both N- and C-terminal cytoplasmic tails | journal = The Journal of Biological Chemistry | volume = 271 | issue = 37 | pages = 22315–20 | date = September 1996 | pmid = 8798390 | doi = 10.1074/jbc.271.37.22315 | doi-access = free }}</ref>

Based on the crystal structure of the homologous [[SCARB2]], a model of the extracellular domain of CD36 has been produced.<ref>{{cite journal | vauthors = Neculai D, Schwake M, Ravichandran M, Zunke F, Collins RF, Peters J, Neculai M, Plumb J, Loppnau P, Pizarro JC, Seitova A, Trimble WS, Saftig P, Grinstein S, Dhe-Paganon S | display-authors = 6 | title = Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36 | journal = Nature | volume = 504 | issue = 7478 | pages = 172–6 | date = December 2013 | pmid = 24162852 | doi = 10.1038/nature12684 | bibcode = 2013Natur.504..172N | s2cid = 4395239 }}</ref> Like SCARB2, CD36 is proposed to contain an [[antiparallel (biochemistry)#Beta sheet|antiparallel]] β-barrel core with many short α-helices adorning it. The structure is predicted to contain a hydrophobic transport tunnel. 
Disulfide linkages between 4 of the 6 [[cysteine]] residues in the extracellular loop are required for efficient intracellular processing and transport of CD36 to the [[plasma membrane]].<ref name="pmid9371725">{{cite journal | vauthors = Gruarin P, Sitia R, Alessio M | title = Formation of one or more intrachain disulphide bonds is required for the intracellular processing and transport of CD36 | journal = The Biochemical Journal | volume = 328 | issue = 2 | pages = 635–42 | date = December 1997 | pmid = 9371725 | pmc = 1218965 | doi = 10.1042/bj3280635 }}</ref> It is not clear what role these linkages play on the function of the mature CD36 protein on the cell surface.

=== Posttranslational modification ===

Besides glycosylation, additional [[post-translational modification]]s have been reported for CD36. CD36 is modified with 4 [[palmitoyl chains]], 2 on each of the two intracellular domains.<ref name="pmid8798390"/> The function of these lipid modifications is currently unknown but they likely promote the association of CD36 with the membrane and possibly [[lipid rafts]] which appear to be important for some CD36 functions.<ref name="pmid12947091">{{cite journal | vauthors = Zeng Y, Tao N, Chung KN, Heuser JE, Lublin DM | title = Endocytosis of oxidized low density lipoprotein through scavenger receptor CD36 utilizes a lipid raft pathway that does not require caveolin-1 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 46 | pages = 45931–6 | date = November 2003 | pmid = 12947091 | doi = 10.1074/jbc.M307722200 | doi-access = free }}</ref><ref name="pmid15496455">{{cite journal | vauthors = Pohl J, Ring A, Korkmaz U, Ehehalt R, Stremmel W | title = FAT/CD36-mediated long-chain fatty acid uptake in adipocytes requires plasma membrane rafts | journal = Molecular Biology of the Cell | volume = 16 | issue = 1 | pages = 24–31 | date = January 2005 | pmid = 15496455 | pmc = 539148 | doi = 10.1091/mbc.E04-07-0616 }}</ref> CD36 could be also phosphorylated at Y62, T92, T323,<ref name="urlwww.phosphosite.org">{{cite web | url = http://www.phosphosite.org/proteinAction.do?id=18224&showAllSites=true | title = CD36 (human) protein page |vauthors=Hornbeck PV, Kornhauser JM, Tkachev S, Zhang B, Skrzypek E, Murray B, Latham V, Sullivan M | work = PhosphoSitePlus | publisher = Cell Signaling Technology, Inc. }}</ref> ubiquitinated at K56, K469, K472 and acetylated at K52, K56, K166, K231, K394, K398, K403.<ref name="pmid18353783">{{cite journal | vauthors = Smith J, Su X, El-Maghrabi R, Stahl PD, Abumrad NA | title = Opposite regulation of CD36 ubiquitination by fatty acids and insulin: effects on fatty acid uptake | journal = The Journal of Biological Chemistry | volume = 283 | issue = 20 | pages = 13578–85 | date = May 2008 | pmid = 18353783 | pmc = 2376227 | doi = 10.1074/jbc.M800008200 | doi-access = free }}</ref><ref name="pmid23603908">{{cite journal | vauthors = Kuda O, Pietka TA, Demianova Z, Kudova E, Cvacka J, Kopecky J, Abumrad NA | title = Sulfo-N-succinimidyl oleate (SSO) inhibits fatty acid uptake and signaling for intracellular calcium via binding CD36 lysine 164: SSO also inhibits oxidized low density lipoprotein uptake by macrophages | journal = The Journal of Biological Chemistry | volume = 288 | issue = 22 | pages = 15547–55 | date = May 2013 | pmid = 23603908 | pmc = 3668716 | doi = 10.1074/jbc.M113.473298 | doi-access = free }}</ref><ref name="pmid22902405">{{cite journal | vauthors = Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV | display-authors = 6 | title = Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns | journal = Cell Reports | volume = 2 | issue = 2 | pages = 419–31 | date = August 2012 | pmid = 22902405 | pmc = 4103158 | doi = 10.1016/j.celrep.2012.07.006 }}</ref>

=== Protein-protein interactions ===

In the absence of ligand, membrane bound CD36 exists primarily in a monomeric state. However exposure to the [[thrombospondin]] ligand causes CD36 to dimerize. This dimerization has been proposed to play an important role in CD36 [[signal transduction]].<ref name="pmid9268192">{{cite journal | vauthors = Daviet L, Malvoisin E, Wild TF, McGregor JL | title = Thrombospondin induces dimerization of membrane-bound, but not soluble CD36 | journal = Thrombosis and Haemostasis | volume = 78 | issue = 2 | pages = 897–901 | date = August 1997 | pmid = 9268192 | doi = 10.1055/s-0038-1657649 | s2cid = 43232897 }}</ref>