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Papers In Press, published online ahead of print September 16, 2002
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Submitted on September 9, 2002
Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY 11203
Corresponding Author: mahmood.hussain{at}downstate.edu
Apolipoprotein B (apoB) is a structural protein and microsomal triglyceride transfer protein (MTP) is a lipid transfer protein. Both are necessary for lipoprotein assembly. ApoB has been proposed to consist of five secondary structural domains, âá1-â1-á2-â2-á3. MTP has been proposed to contain three structural domains (N-terminal â-barrel, central á-helix, and C-terminal lipid cavity) and three functional motifs (lipid transfer, membrane associating, and apoB binding). Several studies have established that MTP’s lipid transfer activity is required for the assembly of lipoproteins. This activity renders nascent apoB secretion-competent and may play a role in the import of triglycerides into the lumen of the endoplasmic reticulum. In addition, MTP binds to apoB. This review discusses specific molecular interactions between apoB and MTP and their role in lipoprotein biosynthesis. ApoB and MTP bind with high affinity involving ionic interactions. MTP interacts at multiple sites in the N-terminal âá1 structural domain of apoB. A novel antagonist that inhibits apoB-MTP binding decreases apoB secretion. Furthermore, site-directed mutagenesis and deletion analyses indicate that apoB-MTP binding may be important for lipoprotein assembly. 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.
Revised on September 12, 2002
Accepted on September 13, 2002
Microsomal triglyceride transfer protein and its role in apolipoprotein B-assembly
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