Comparative Studies of Vertebrate Platelet Glycoprotein 4 (CD36).

Roger S Holmes

doi:10.3390/biom2030389

Abstract

Platelet glycoprotein 4 (CD36) (or fatty acyl translocase [FAT], or scavenger receptor class B, member 3 [SCARB3]) is an essential cell surface and skeletal muscle outer mitochondrial membrane glycoprotein involved in multiple functions in the body. CD36 serves as a ligand receptor of thrombospondin, long chain fatty acids, oxidized low density lipoproteins (LDLs) and malaria-infected erythrocytes. CD36 also influences various diseases, including angiogenesis, thrombosis, atherosclerosis, malaria, diabetes, steatosis, dementia and obesity. Genetic deficiency of this protein results in significant changes in fatty acid and oxidized lipid uptake. Comparative CD36 amino acid sequences and structures and CD36 gene locations were examined using data from several vertebrate genome projects. Vertebrate CD36 sequences shared 53–100% identity as compared with 29–32% sequence identities with other CD36-like superfamily members, SCARB1 and SCARB2. At least eight vertebrate CD36 N-glycosylation sites were conserved which are required for membrane integration. Sequence alignments, key amino acid residues and predicted secondary structures were also studied. Three CD36 domains were identified including cytoplasmic, transmembrane and exoplasmic sequences. Conserved sequences included N- and C-terminal transmembrane glycines; and exoplasmic cysteine disulphide residues; TSP-1 and PE binding sites, Thr92 and His242, respectively; 17 conserved proline and 14 glycine residues, which may participate in forming CD36 ‘short loops’; and basic amino acid residues, and may contribute to fatty acid and thrombospondin binding. Vertebrate CD36 genes usually contained 12 coding exons. The human CD36 gene contained transcription factor binding sites (including PPARG and PPARA) contributing to a high gene expression level (6.6 times average). Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate CD36 gene with vertebrate SCARB1 and SCARB2 genes. These suggested that CD36 originated in an ancestral genome and was subsequently duplicated to form three vertebrate CD36 gene family members, SCARB1, SCARB2 and CD36.

Highlights

Platelet glycoprotein 4 (CD36) is one of at least three members of the CD36-like family that is an integral membrane protein of many tissues of the body which plays a role in fatty acyl translocation and as a multiple ligand cell surface receptor of oxidized low density lipoproteins (LDLs) lipoproteins, long chain fatty acids, aged neutrophils and Plasmodium falciparum-parasitized erythrocytes (PE)which has been implicated in several diseases including insulin resistance, diabetes, atherosclerosis and malaria [1,2,3,4,5,6,7,8,9,10]
The deduced amino acid sequences for cow (Bos taurus), opossum (Monodelphis domestica), chicken (Gallus gallus), frog (Xenopus tropicalis) and zebrafish (Danio rerio) CD36 are shown in Figure 1 together with previously reported sequences for human and mouse CD36 (Table 1) [45,46]
CD36 has a unique property among these proteins in serving a major role in fatty acyl translocation and as a multiple ligand cell surface receptor of oxidized LDL lipoproteins, long chain fatty acids, aged neutrophils and Plasmodium falciparum-parasitized erythrocytes [3,4,5,6,7,8,9,10]

Summary

Introduction

Platelet glycoprotein 4 (CD36) (cluster of differentiation 36) (or fatty acyl translocase [FAT]; and scavenger receptor class B, member 3 [SCARB3]) is one of at least three members of the CD36-like family that is an integral membrane protein of many tissues of the body which plays a role in fatty acyl translocation and as a multiple ligand cell surface receptor of oxidized LDL lipoproteins (ox-LDL), long chain fatty acids, aged neutrophils and Plasmodium falciparum-parasitized erythrocytes (PE)which has been implicated in several diseases including insulin resistance, diabetes, atherosclerosis and malaria [1,2,3,4,5,6,7,8,9,10]. Platelet glycoprotein 4 (CD36) (cluster of differentiation 36) (or fatty acyl translocase [FAT]; and scavenger receptor class B, member 3 [SCARB3]) is one of at least three members of the CD36-like family that is an integral membrane protein of many tissues of the body which plays a role in fatty acyl translocation and as a multiple ligand cell surface receptor of oxidized LDL lipoproteins (ox-LDL), long chain fatty acids, aged neutrophils and Plasmodium falciparum-parasitized erythrocytes (PE). SCARB1 ( called CLA1, SRB1 and CD36L1), a second member of the CD36-like family, is a homo-oligomeric plasma membrane cell surface glycoprotein receptor for high density lipoprotein cholesterol (HDL), other phospholipid ligands and chylomicron remnants [16,17,18,19,20]. SCARB2 ( called LIMP2 (lysosomal integral membrane protein), SRB2 and CD36L2) is a third member of the CD36 family predominantly integrated within lysosomal and endosomal membranes which contributes to lysosomal membrane organization and transport functions [21,22,23,24,25]

Methods

Results

Conclusion