The non-specific lipid-transfer protein (sterol carrier protein 2) and its relationship to peroxisomes.
The non-specific lipid-transfer protein (nsL-TP), also known as sterol carrier protein 2 (SCP2), is a small (M(r) 13,000) basic protein which catalyzes in vitro the transfer of a great variety of lipids, including cholesterol, between membranes. Inherent to this transfer activity, the protein stimulates in vitro various aspects of cholesterol metabolism. nsL-TP is synthesized as a precursor (pre-nsL-TP) with a leader sequence of 20 amino acid residues. It appears that the peroxisomes play an important role in the conversion of pre-nsL-TP into the mature form. In fact, nsL-TP appears to be mainly present in peroxisomes as shown by immunogold labeling of rat liver, adrenals and testes using the anti-nsL-TP antibody. However, interpretation of the data is complicated by the fact that the antibody raised against nsL-TP also reacts with a protein with a M(r) of 58,000. From cDNA analysis it became apparent that the cross-reactive 58-kDa protein contains the complete sequence of pre-nsL-TP at its C-terminus. However, pre-nsL-TP and the 58-kDa protein are synthesized from different mRNAs. Interestingly, the N-terminal part of the 58-kDa protein was found to have significant sequence similarity with 3-oxoacyl-CoA thiolase. Both pre-nsL-TP and the 58-kDa protein contain the C-terminal peroxisomal targeting tripeptide Ala-Lys-Leu. However, as shown by subcellular fractionation studies the 58-kDa protein is exclusively localized in the peroxisomes whilst nsL-TP is not only detected in the peroxisomes but also in other subcellular fractions. Moreover, a membrane-bound form of nsL-TP was detected. This membrane-bound form is present at the cytosolic side of the membranes. The physiological function of nsL-TP is still unclear; some recent developments are discussed briefly in the last part of this review.
Institute for Biomembranes/Centre for Biomembranes and Lipid Enzymology, Utrecht University, Netherlands.
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BC
Ossendorp
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KW
Wirtz
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D004247:DNA / Q000032:analysis; D008830:Microbodies / Q000502:physiology*; D008969:Molecular Sequence Data; D010940:Plant Proteins; D051381:Rats; D016415:Sequence Alignment; D013347:Subcellular Fractions / Q000737:chemistry
D002352:Carrier Proteins; D010940:Plant Proteins; C072087:sterol carrier proteins; D004247:DNA