Apolipoprotein B: structure, biosynthesis and role in the lipoprotein assembly process

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Apolipoprotein B (apoB) is crucial for lipoprotein structure and function.
• Two main species, apoB 100 (liver-synthesized) and apoB 48 (intestine-derived), exist.
• Understanding their structure and synthesis is vital for lipid metabolism research.

Purpose of the Study:

• To elucidate the complete amino acid sequence of apoB 100.
• To investigate the structural features important for lipid binding.
• To model the assembly and post-translational modifications of apoB 100 and apoB 48.

Main Methods:

• Cloning and sequencing of complementary DNA (cDNA) for apoB 100.
• Analysis of amino acid sequence for structural motifs.
• Examination of protein synthesis and modification pathways in cellular compartments (ER, Golgi).

Main Results:

• The complete sequence of apoB 100 (4536 amino acids + signal sequence) was determined.
• Specific structural features (hydrophobic sequences, beta-sheets, amphipathic helices) are implicated in lipid binding.
• ApoB 100 undergoes rapid synthesis, secretion, N-glycosylation, and lipid modification within the ER and Golgi.
• ApoB 48 is a truncated form (48% of apoB 100) synthesized in the intestine, likely not via proteolysis or alternative splicing of apoB 100 mRNA.

Conclusions:

• The detailed structure of apoB 100 provides insights into its function in lipoprotein assembly.
• A model for apoB 100 lipoprotein assembly is proposed.
• The synthesis of apoB 48 appears distinct from apoB 100, with current evidence not supporting alternative splicing as the mechanism.