Microsomal triglyceride transfer protein (MTP) is a heterodimeric
protein that transfers neutral
lipids between membranes in vitro. Absence of this
lipid transfer activity in the microsomes of
abetalipoproteinemia patients established its pivotal function in
lipoprotein assembly. Recent studies indicate that the
lipid transfer activity is involved in importing
triglycerides into the lumen of the endoplasmic reticulum. In addition to its
lipid transfer activity, MTP physically interacts with
apoB. This led to speculation that MTP may act as a chaperone. It remains to be determined whether the binding of MTP to
apoB plays a role in either proper folding or net lipidation of nascent
apoB. Both functions,
lipid transfer and
apoB binding, may be involved in the initial step of lipidation of nascent
apoB resulting in the synthesis of primordial
lipoprotein particles. Furthermore, it has been shown that MTP stably associates with
lipid vesicles. The
lipid-associated MTP may be important in core expansion of primordial
lipoproteins. In summary, three independent functions (
lipid transfer,
apoB binding and membrane association) of MTP have been identified. Here, we propose these functions are carried out by a combination of different structural motifs. Based on sequence homology with
lipovitellin, the M subunit of MTP is predicted to contain three beta-sheets (A, C, and N) and
one alpha-helical domain. The A- and C-sheets may be involved in
lipid transfer, the N-sheet and the helical domain in
apoB binding, and the N- and A-sheets in membrane association. It is also speculated that MTP may function in physiologic processes beyond
lipoprotein assembly.