Apolipoprotein B binding to microsomal triglyceride transfer protein decreases with increases in length and lipidation: implications in lipoprotein biosynthesis
- PMID: 9335568
- DOI: 10.1021/bi971395a
Apolipoprotein B binding to microsomal triglyceride transfer protein decreases with increases in length and lipidation: implications in lipoprotein biosynthesis
Abstract
Microsomal triglyceride transfer protein (MTP), a heterodimer of 97 kDa and protein disulfide isomerase, is required for the assembly of apolipoprotein B (apoB)-containing triglyceride-rich lipoproteins. These proteins have been shown to interact with each other during early stages of lipoprotein biosynthesis. Our studies indicated that binding between apoB and heterodimeric MTP was of high affinity (Kd 10-30 nM) due to ionic interactions. In contrast to MTP, protein disulfide isomerase alone interacted very poorly with lipoproteins, indicating the importance of the heterodimer in these bindings. Preincubation of lipoproteins with detergents enhanced their interaction with MTP. Native VLDL bound poorly to MTP, but its preincubation with Tween-20 resulted in significantly increased binding to MTP. Furthermore, binding of LDL was enhanced by preincubation with taurocholate, indicating that partial delipidation of apoB-containing lipoproteins results in increased binding to MTP. Subsequently, attempts were made to study interactions between C-terminally truncated apoB polypeptides and MTP. Binding of all the polypeptides to MTP was enhanced in the presence of taurocholate. Comparisons revealed that the binding of different apoB polypeptides to MTP was in the order of apoB18 > apoB28 > apoB42 > apoB100. These studies indicated that optimum interactions occur between apoB18 and MTP, and that the increase in apoB length beyond apoB18 has a negative effect on these interactions. Since apoB18 does not assemble triglyceride-rich lipoproteins, these studies suggest that apoB may interact with MTP before its lipidation. It is proposed that steps in lipoprotein biosynthesis may be dictated by the sequential display of different functional domains on the apoB polypeptide.
Similar articles
-
Lysine and arginine residues in the N-terminal 18% of apolipoprotein B are critical for its binding to microsomal triglyceride transfer protein.Biochemistry. 1998 Mar 17;37(11):3727-34. doi: 10.1021/bi972629t. Biochemistry. 1998. PMID: 9521691
-
Binding of microsomal triglyceride transfer protein to lipids results in increased affinity for apolipoprotein B: evidence for stable microsomal MTP-lipid complexes.J Biol Chem. 2001 Aug 17;276(33):31466-73. doi: 10.1074/jbc.M100390200. Epub 2001 Jun 26. J Biol Chem. 2001. PMID: 11427523
-
The microsomal triglyceride transfer protein facilitates assembly and secretion of apolipoprotein B-containing lipoproteins and decreases cotranslational degradation of apolipoprotein B in transfected COS-7 cells.J Biol Chem. 1996 Jun 14;271(24):14124-33. J Biol Chem. 1996. PMID: 8662886
-
Progress towards understanding the role of microsomal triglyceride transfer protein in apolipoprotein-B lipoprotein assembly.Biochim Biophys Acta. 2000 Jun 26;1486(1):72-83. doi: 10.1016/s1388-1981(00)00049-4. Biochim Biophys Acta. 2000. PMID: 10856714 Review.
-
Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly.J Lipid Res. 2003 Jan;44(1):22-32. doi: 10.1194/jlr.r200014-jlr200. J Lipid Res. 2003. PMID: 12518019 Review.
Cited by
-
Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.Science. 2023 Sep;381(6661):eadh5207. doi: 10.1126/science.adh5207. Epub 2023 Sep 1. Science. 2023. PMID: 37651538
-
APOB CRISPR-Cas9 Engineering in Hypobetalipoproteinemia: A Promising Tool for Functional Studies of Novel Variants.Int J Mol Sci. 2022 Apr 13;23(8):4281. doi: 10.3390/ijms23084281. Int J Mol Sci. 2022. PMID: 35457099 Free PMC article.
-
Eruptive xanthoma model reveals endothelial cells internalize and metabolize chylomicrons, leading to extravascular triglyceride accumulation.J Clin Invest. 2021 Jun 15;131(12):e145800. doi: 10.1172/JCI145800. J Clin Invest. 2021. PMID: 34128469 Free PMC article.
-
The Nuclear Envelope in Lipid Metabolism and Pathogenesis of NAFLD.Biology (Basel). 2020 Oct 15;9(10):338. doi: 10.3390/biology9100338. Biology (Basel). 2020. PMID: 33076344 Free PMC article. Review.
-
Endoplasmic reticulum quality control in lipoprotein metabolism.Mol Cell Endocrinol. 2019 Dec 1;498:110547. doi: 10.1016/j.mce.2019.110547. Epub 2019 Aug 20. Mol Cell Endocrinol. 2019. PMID: 31442546 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous