Structure and function of cholesteryl ester transfer protein in the tree shrew

Lipids. 2011 Jul;46(7):607-16. doi: 10.1007/s11745-011-3552-2. Epub 2011 Apr 1.

Abstract

Cholesteryl ester transfer protein (CETP) plays an important role in reverse cholesterol transport (RCT). To study on the structure and function of CETP in the tree shrew, a kind of animal resistant to atherosclerosis, we completed the cloning of the full-length tree-shrew CETP cDNA sequence based on the reported partial sequence. The full-length cDNA of tree shrew CETP was 1,704 bp and the deduced protein of the cDNA showed a sequence identity of 81, 80 and 74%, respectively, with the human, monkey and rabbit CETP. The level of CETP mRNA in the liver was much more abundant than that in the other tissues. A mutant protein with a substitution of Asn at position 110 by Gln was found to possess an impaired secretion property compared with the wild-type tree shrew CETP. The mutant proteins, respectively, with a substitution of Pro at position 344 by Ser and a substitution of Gln at position 452 by Arg displayed similar secretion ability, but a decreased cholesteryl ester transfer capability compared with the wild type (48 and 26% lower, respectively). These findings demonstrate that liver is the main tissue synthesizing CETP in the tree shrew. Asn at position 110 plays an important role in the secretion of tree shrew CETP. The residues at position 344 and 452 play essential roles in cholesteryl ester transferring process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Cholesterol Ester Transfer Proteins / chemistry
  • Cholesterol Ester Transfer Proteins / genetics*
  • Cholesterol Ester Transfer Proteins / metabolism*
  • DNA, Complementary / genetics
  • DNA, Complementary / metabolism
  • Liver / metabolism*
  • Male
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tissue Distribution
  • Transfection
  • Tupaiidae / metabolism*

Substances

  • Cholesterol Ester Transfer Proteins
  • DNA, Complementary
  • RNA, Messenger