Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly

被引:452
作者
Hussain, MM
Shi, J
Dreizen, P
机构
[1] Suny Downstate Med Ctr, Dept Anat & Cell Biol, Brooklyn, NY 11203 USA
[2] Suny Downstate Med Ctr, Dept Pediat, Brooklyn, NY 11203 USA
[3] Suny Downstate Med Ctr, Med Biophys Div, Brooklyn, NY 11203 USA
关键词
protein-protein interactions; protein motifs; domains; abetalipoproteinemia; hypobetalipoproteinemia; apolipoprotein B; MTP;
D O I
10.1194/jlr.R200014-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) are necessary for lipoprotein assembly. ApoB consists of five structural domains, betaalpha(1)-beta(1)-alpha(2)-beta(2)-alpha(3). We propose that MTP contains three structural motifs (N-terminal beta-barrel, central alpha-helix, and C-terminal lipid cavity) and three functional domains (lipid transfer, membrane associating, and apoB binding). MTP's lipid transfer activity is required for the assembly of lipoproteins. This activity renders nascent apoB secretion-competent and may be involved in the import of tri-glycerides into the lumen of endoplasmic reticulum. In addition, MTP binds to apoB with high affinity involving ionic interactions. MTP interacts at multiple sites in the N-terminal betaalpha(1) structural domain of apoB. A novel antagonist that inhibits apoB-MTP binding decreases apoB secretion. Furthermore, site-directed mutagenesis and deletion analyses that inhibit apoB-MTP binding decrease apoB secretion. Lipids modulate protein-protein interactions between apoB and MTP. Lipids associated with MTP increase apoB-MTP binding whereas lipids associated with apoB decrease this binding. Thus, specific antagonist, site-directed mutagenesis, deletion analyses, and modulation studies support the notion that apoB-MTP binding plays a role in lipoprotein biogenesis. However, specific steps in lipoprotein assembly that require apoB-MTP binding have not been identified. ApoB-MTP binding may be important for the prevention of degradation and lipidation of nascent apoB.
引用
收藏
页码:22 / 32
页数:11
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