Apolipoprotein B and low-density lipoprotein structure: implications for biosynthesis of triglyceride-rich lipoproteins

Adv Protein Chem. 1994:45:205-48. doi: 10.1016/s0065-3233(08)60641-5.

Abstract

ApoB100 is a very large glycoprotein essential for triglyceride transport in vertebrates. It plays functional roles in lipoprotein biosynthesis in liver and intestine, and is the ligand recognized by the LDL receptor during receptor-mediated endocytosis. ApoB100 is encoded by a single gene on chromosome 2, and the message undergoes a unique processing event to form apoB48 message in the human intestine, and, in some species, in liver as well. The primary sequence is relatively unique and appears unrelated to the sequences of other serum apolipoproteins, except for some possible homology with the receptor recognition sequence of apolipoprotein E. From its sequence, structure prediction shows the presence of both sheet and helix scattered along its length, but no transmembrane domains apart from the signal sequence. The multiple carbohydrate attachment sites have been identified, as well as the locations of most of its disulfides. ApoB is the single protein found on LDL. These lipoproteins are emulsion particles, containing a core of nonpolar cholesteryl ester and triglyceride oil, surrounded by an emulsifying agent, a monolayer of phospholipid, cholesterol, and a single molecule of apoB100. An emulsion particle model is developed to predict accurately the physical and compositional properties of an LDL of any given size. A variety of techniques have been employed to map apoB100 on the surface of the LDL, and all yield a model in which apoB surrounds the LDL like a belt. Moreover, it is concluded that apoB100 folds into a long, flexible structure with a cross-section of about 20 x 54 A2 and a length of about 585 A. This structure is embedded in the surface coat of the LDL and makes contact with the core. During lipoprotein biosynthesis in tissue culture, truncated fragments of apoB100 are secreted on lipoproteins. Here, it was found that the lipoprotein core circumference was directly proportional to the apoB fragment size. A cotranslational model has been porposed for the lipoprotein assembly, which includes these structural features, and it is concluded that in permanent hepatocyte cell lines, apoB size determines lipoprotein core circumference.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apolipoproteins B / chemistry*
  • Apolipoproteins B / metabolism*
  • Humans
  • Lipoproteins, LDL / chemistry*
  • Lipoproteins, LDL / metabolism*
  • Molecular Sequence Data
  • Triglycerides / biosynthesis*
  • Triglycerides / chemistry

Substances

  • Apolipoproteins B
  • Lipoproteins, LDL
  • Triglycerides