A mechanism of membrane neutral lipid acquisition by the microsomal triglyceride transfer protein

J Biol Chem. 2000 Sep 29;275(39):30372-7. doi: 10.1074/jbc.C000364200.


The microsomal triglyceride transfer protein (MTP) and apolipoprotein B (apoB) belong to the vitellogenin (VTG) family of lipid transfer proteins. MTP is essential for the intracellular assembly and secretion of apoB-containing lipoproteins, the key intravascular lipid transport proteins in vertebrates. We report the predicted three-dimensional structure of the C-terminal lipid binding cavity of MTP, modeled on the crystal structure of the lamprey VTG gene product, lipovitellin. The cavity in MTP resembles those found in the intracellular lipid-binding proteins and bactericidal/permeability-increasing protein. Two conserved helices, designated A and B, at the entrance to the MTP cavity mediate lipid acquisition and binding. Helix A (amino acids 725-736) interacts with membranes in a manner similar to viral fusion peptides. Mutation of helix A blocks the interaction of MTP with phospholipid vesicles containing triglyceride and impairs triglyceride binding. Mutations of helix B (amino acids 781-786) and of N780Y, which causes abetalipoproteinemia, have no impact on the interaction of MTP with phospholipid vesicles but impair triglyceride binding. We propose that insertion of helix A into lipid membranes is necessary for the acquisition of neutral lipids and that helix B is required for their transfer to the lipid binding cavity of MTP.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apolipoproteins B / chemistry
  • Binding Sites
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Chylomicrons / metabolism
  • Computer Simulation
  • Egg Proteins
  • Egg Proteins, Dietary
  • Lipid Bilayers / metabolism
  • Lipoproteins, VLDL / metabolism
  • Membrane Lipids / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Phospholipids / metabolism
  • Protein Disulfide-Isomerases / metabolism*
  • Sequence Homology, Amino Acid
  • Vitellogenins / chemistry


  • Apolipoproteins B
  • Carrier Proteins
  • Chylomicrons
  • Egg Proteins
  • Egg Proteins, Dietary
  • Lipid Bilayers
  • Lipoproteins, VLDL
  • Membrane Lipids
  • Phospholipids
  • Vitellogenins
  • microsomal triglyceride transfer protein
  • lipovitellin
  • Protein Disulfide-Isomerases