Arteriosclerosis, Vol 10, 95-105, Copyright © 1990 by American Heart Association

ARTICLES

Use of synthetic peptide analogues to localize lecithin:cholesterol acyltransferase activating domain in apolipoprotein A-I

GM Anantharamaiah, YV Venkatachalapathi, CG Brouillette and JP Segrest
Department of Medicine, University of Alabama Medical Center, Birmingham 35294.

The major protein of high density lipoprotein (HDL), apolipoprotein (apo) A-I, is the major activator of the plasma enzyme lecithin:cholesterol acyltransferase (LCAT). A consensus amino acid sequence has been defined for the eight, 22-residue long, tandem amphipathic helical repeats located in the carboxy-terminal region of apo A-I. A series of 22 and 44mer synthetic peptide analogues of the consensus domain, differing only in their 13th amino acid residue, were prepared and tested for LCAT activation. One of the peptides was found to equal apo A-I in LCAT activation. This is the first time a peptide activator for LCAT that rivals the activity of apo A-I in the vesicular and discoidal egg phosphatidylcholine assay systems has been synthesized. Based on these results, we propose that the major LCAT- activating domain of apo A-I resides in the 22mer tandem repeats, each containing Glu at the 13th residue and located between residues 66 and 121 in the native apolipoprotein.

This article has been cited by other articles:

				G. M. Anantharamaiah, V. K. Mishra, D. W. Garber, G. Datta, S. P. Handattu, M. N. Palgunachari, M. Chaddha, M. Navab, S. T. Reddy, J. P. Segrest, et al. Structural requirements for antioxidative and anti-inflammatory properties of apolipoprotein A-I mimetic peptides J. Lipid Res., September 1, 2007; 48(9): 1915 - 1923. [Abstract] [Full Text] [PDF]

				G. Datta, M. Chaddha, S. Hama, M. Navab, A. M. Fogelman, D. W. Garber, V. K. Mishra, R. M. Epand, R. F. Epand, S. Lund-Katz, et al. Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide J. Lipid Res., July 1, 2001; 42(7): 1096 - 1104. [Abstract] [Full Text] [PDF]

				P. G. Frank and Y. L. Marcel Apolipoprotein A-I: structure;-function relationships J. Lipid Res., June 1, 2000; 41(6): 853 - 872. [Abstract] [Full Text]

				D. C. McManus, B. R. Scott, P. G. Frank, V. Franklin, J. R. Schultz, and Y. L. Marcel Distinct Central Amphipathic alpha -Helices in Apolipoprotein A-I Contribute to the in Vivo Maturation of High Density Lipoprotein by Either Activating Lecithin-Cholesterol Acyltransferase or Binding Lipids J. Biol. Chem., February 18, 2000; 275(7): 5043 - 5051. [Abstract] [Full Text] [PDF]

				M. G. Sorci-Thomas, L. Curtiss, J. S. Parks, M. J. Thomas, M. W. Kearns, and M. Landrum The Hydrophobic Face Orientation of Apolipoprotein A-I Amphipathic Helix Domain 143-164 Regulates Lecithin:Cholesterol Acyltransferase Activation J. Biol. Chem., May 8, 1998; 273(19): 11776 - 11782. [Abstract] [Full Text] [PDF]

				A. Dhoest, Z. Zhao, B. De Geest, E. Deridder, A. Sillen, Y. Engelborghs, D. Collen, and P. Holvoet Role of the Arg123-Tyr166 Paired Helix of Apolipoprotein A-I in Lecithin:Cholesterol Acyltransferase Activation J. Biol. Chem., June 20, 1997; 272(25): 15967 - 15972. [Abstract] [Full Text] [PDF]

				H. Campos, J. Lopez-Miranda, C. Rodriguez, M. Albajar, E. J. Schaefer, and J. M. Ordovas Urbanization Elicits a More Atherogenic Lipoprotein Profile in Carriers of the Apolipoprotein A-IV-2 Allele Than in A-IV-1 Homozygotes Arterioscler. Thromb. Vasc. Biol., June 1, 1997; 17(6): 1074 - 1081. [Abstract] [Full Text]

				M. G. Sorci-Thomas, L. Curtiss, J. S. Parks, M. J. Thomas, and M. W. Kearns Alteration in Apolipoprotein A-I 22-Mer Repeat Order Results in a Decrease in Lecithin:Cholesterol Acyltransferase Reactivity J. Biol. Chem., March 14, 1997; 272(11): 7278 - 7284. [Abstract] [Full Text] [PDF]

				G. W. Buchko, W. D. Treleaven, S. J. Dunne, A. S. Tracey, and R. J. Cushley Structural Studies of a Peptide Activator of Human Lecithin-Cholesterol Acyltransferase J. Biol. Chem., February 9, 1996; 271(6): 3039 - 3045. [Abstract] [Full Text] [PDF]

				M. N. Palgunachari, V. K. Mishra, S. Lund-Katz, M. C. Phillips, S. O. Adeyeye, S. Alluri, G.M. Anantharamaiah, and J. P. Segrest Only the Two End Helixes of Eight Tandem Amphipathic Helical Domains of Human Apo A-I Have Significant Lipid Affinity : Implications for HDL Assembly Arterioscler. Thromb. Vasc. Biol., February 1, 1996; 16(2): 328 - 338. [Abstract] [Full Text]

				J. Bergeron, P. G. Frank, D. Scales, Q.-H. Meng, G. Castro, and Y. L. Marcel Apolipoprotein A-I Conformation in Reconstituted Discoidal Lipoproteins Varying in Phospholipid and Cholesterol Content J. Biol. Chem., November 17, 1995; 270(46): 27429 - 27438. [Abstract] [Full Text] [PDF]

				V. K. Mishra, M. N. Palgunachari, S. Lund-Katz, M. C. Phillips, J. P. Segrest, and G. M. Anantharamaiah Effect of the Arrangement of Tandem Repeating Units of Class A Amphipathic alpha-Helixes on Lipid Interaction J. Biol. Chem., January 27, 1995; 270(4): 1602 - 1611. [Abstract] [Full Text] [PDF]