Lipid-free Apolipoprotein A-I Structure Insights into HDL Formation and Atherosclerosis Development》.pdfVIP

Archives of Medical Research 46 (2015) 351e360 REVIEW ARTICLE Lipid-free Apolipoprotein A-I Structure: Insights into HDL Formation and Atherosclerosis Development Xiaohu Mei and David Atkinson Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts, USA Received for publication May 21, 2015; accepted May 27, 2015 (ARCMED-D-15-00365). Apolipoprotein A-I is the major protein in high-density lipoprotein (HDL) and plays an important role during the process of reverse cholesterol transport (RCT). Knowledge of the high-resolution structure of full-length apoA-I is vital for a molecular understanding of the function of HDL at the various steps of the RCT pathway. Due to the flexible nature of apoA-I and aggregation properties, the structure of full-length lipid-free apoA-I has evaded description for over three decades. Sequence analysis of apoA-I suggested that the amphipathic a-helix is the structural motif of exchangeable apolipoprotein, and NMR, X-ray and MD simulation studies have confirmed this. Different laboratories have used different methods to probe the secondary structure distribution and organization of both the lipid-free and lipid-bound apoA-I structure. Mutation analysis, synthetic peptide models, surface chemistry and crystal structures have converged on the lipid-free apoA-I domain structure and function: the N-terminal domain [1e184] forms a heli