Document Detail


Structure-function studies of human cholesteryl ester transfer protein by linker insertion scanning mutagenesis.
MedLine Citation:
PMID:  2012808     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human plasma cholesteryl ester transfer protein (CETP) enhances transfer and exchange of cholesteryl ester (CE) and triglyceride (TG) between high-density lipoprotein and other lipoproteins. To define regions responsible for the neutral lipid transfer activities at the molecular level, a total of 27 linker insertion mutants at 18 different sites along the CETP molecule were prepared and transiently expressed in a mammalian cell line (COS). The inserted linkers were small (usually 6 bp) and did not interrupt the translational reading frame of the CETP cDNA. Although secretion of each mutant protein was less than that of wild-type CETP, the majority of the mutants had normal cholesteryl ester transfer activity (transfer activity per nanogram of CETP in media). However, insertional alterations in three regions severely impaired CE transfer activity: (1) in the region of amino acids 48-53; (2) at amino acid 165; and (3) in the region of amino acids 373-379. Although the impaired activities could also be a result of globally incorrect folding of these CETP mutants, hydrophobicity analysis and secondary structure predictions tended to exclude this possibility for most of the insertion sites at which insertions resulted in inactivation. The insertion at amino acid 379 occurs immediately after a triplet of lysine residues, suggesting that this region might be involved in an essential step in the mechanism of CE and TG transfer, such as the binding of CETP to phosphatidylcholine molecules in the lipoprotein surface. Effects on TG transfer activity were generally similar to those on CE transfer activity, suggesting a similar structural requirement for both neutral lipid transfer activities.
Authors:
S Wang; L P Deng; M L Brown; L B Agellon; A R Tall
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemistry     Volume:  30     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  1991 Apr 
Date Detail:
Created Date:  1991-05-13     Completed Date:  1991-05-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3484-90     Citation Subset:  IM    
Affiliation:
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Carrier Proteins / genetics*
Cell Line
Cholesterol Ester Transfer Proteins
Cholesterol Esters / metabolism
DNA / metabolism
Glycoproteins*
Humans
Molecular Sequence Data
Mutagenesis
Protein Conformation
Structure-Activity Relationship*
Triglycerides / metabolism
Grant Support
ID/Acronym/Agency:
HL22682/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/CETP protein, human; 0/Carrier Proteins; 0/Cholesterol Ester Transfer Proteins; 0/Cholesterol Esters; 0/Glycoproteins; 0/Triglycerides; 9007-49-2/DNA

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