화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.441, No.2, 469-475, 2013
Lecithin cholesterol acyltransferase (LCAT) activity in the presence of Apo-AI-derived peptides exposed to disorder-order conformational transitions
Although the association of Apo Al with HDLs has been proposed to activate LCAT activity, the detailed molecular mechanisms involved in the process are not known. Therefore, in this study we have investigated how conformational changes in several exposed regions of Apo-Al might cause LCAT activation and for this purpose, designed a strategy to investigate three Apo Al-derived peptides. Since these peptides present the ability to adopt several secondary structure conformations, they were used to determine whether LCAT activity could be modulated in the presence of a particular conformation. Circular dichroism experiments showed that Apo AI-derived peptides in PBS displayed a disordered arrangement, with a strong tendency to adopt beta-sheet and random conformational structures as a function of concentration. However, in the presence of Lyso-C12PC, maximal percentages of alpha-helical structures were observed. Performed in human plasma, time-course experiments of LCAT activity under control conditions reached the highest level of H-3-cholesteryl esters after 2.5 h incubation. In the presence of Apo Al-derived peptides, a significant increase in the production of H-3-cholesteryl esters was observed. The present study provides an important insight into the potential interactions between LCAT and lipoproteins and also suggests that peptides, initially present in a disordered conformation, are able to sense the lipid environment provided by lipoproteins of plasma and following a disorder-to-order transition, change their conformation to an ordered alpha-helix. (C) 2013 Elsevier Inc. All rights reserved.