Natural mutations of apolipoprotein A-I impairing activation of lecithincholesterol acyltransferase》.pdfVIP

Biochimica et Biophysica Acta 1631 (2003) 72– 76 Natural mutations of apolipoprotein A-I impairing activation of lecithin:cholesterol acyltransferase a b,1 b,2 a,* Anh Hoang , Wei Huang , Jun Sasaki , Dmitri Sviridov a Wynn Domain, Baker Medical Research Institute, P.O. Box 6492 St. Kilda Rd. Central, Melbourne, Vic. 8008, Australia b Department of Internal Medicine, Fukuoka University, School of Medicine, 45-1, 7-chome Nanakuma, Jonan, Fukuoka 814-80, Japan Received 16 July 2002; received in revised form 25 October 2002; accepted 14 November 2002 Abstract Five natural mutations of apolipoprotein A-I (apoA-I), apoA-I(A95D), apoA-I(Y100H), apoA-I(E110K), apoA-I(V156E) and apoA- I(H162Q), were studied for their ability to activate lecithin:cholesterol acyltransferase (LCAT). Mutants apoA-I(E110K), apoA-I(V156E) and apoA-I(H162Q) had an impaired ability to activate LCAT. Combined with data on other apoA-I mutants this finding is consistent with the idea that the central region between amino acids 110 and 160 is likely to be the ‘‘active site’’ of apoA-I involved in the interaction with LCAT and that a specific sequence of apoA-I is required for activation of the enzyme. D 2002 Elsevier Science B.V. All rights reserved. Keywords: High density lipoprotein; Apolipoprotein A-I; LCAT 1. Introduction [3–7]. It was demonstrated that the LCAT activating domain