Microsomal triglyceride transfer protein: a multifunctional protein.
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.
Hussain
Mohammed Mahmood
MM
Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, 450 Clarkson Ave, Box 5, Brooklyn, NY 11203, USA. mahmood.hussain@downstate.edu
Iqbal
Jahangir
J
Anwar
Kamran
K
Rava
Paul
P
Dai
Kezhi
K
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D011487:Protein Conformation
D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein