Expression cloning of SR-BI, a CD36-related class B scavenger receptor.
Scavenger receptors are integral membrane proteins that mediate the endocytosis of modified lipoproteins. The first of these to be purified and cloned were the type I and II macrophage scavenger receptors (SR-AI and SR-AII; class A scavenger receptors). Subsequently, the cell surface protein CD36 was shown to bind oxidized low density lipoprotein (oxidized LDL). From a Chinese hamster ovary (CHO) cell variant we have cloned by expression the cDNA for a new member of the CD36 family of membrane proteins, SR-BI, whose predicted protein sequence of 509 amino acids is approximately 30% identical to those of the four previously identified family members. Both SR-BI and CD36 displayed high affinity binding for acetylated LDL with an apparent dissociation constant on the order of approximately 5 micrograms of protein/ml. The ligand binding specificities of CD36 and SR-BI, determined by direct binding or competition assays, were similar, but not identical; both bind modified proteins (acetylated LDL, oxidized LDL, maleylated bovine serum albumin), but not the broad array of other polyanions (e.g. fucoidin, polyguanosinic acid, carrageenan) which are ligands of the class A receptors. Thus, SR-BI and CD36 define a second class of scavenger receptors, designated class B. Native LDL, which does not bind to either class A receptors or CD36, unexpectedly bound with high affinity to SR-BI. Northern blot analysis of murine tissues showed that SR-BI was most abundantly expressed in fat and was present at moderate levels in lung and liver. Furthermore, SR-BI mRNA expression was induced upon differentiation of 3T3-L1 cells into adipocytes. Thus, the tissue distribution of expression and ligand binding properties of SR-BI raise the possibility that this cell surface receptor may play an important role in lipid metabolism.
Acton
S L
SL
Department of Biology, Massachusetts Institute of Technology, Cambridge.
Scherer
P E
PE
Lodish
H F
HF
Krieger
M
M
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D018955:CD36 Antigens; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D018076:DNA, Complementary; D016166:Free Radical Scavengers; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B
D015703:Antigens, CD; D018955:CD36 Antigens; D018076:DNA, Complementary; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; C495139:MSR1 protein, human; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B