Activation of lecithin:cholesterol acyltransferase by HDL ApoA-I central helices.
Lecithin:cholesterol acyltransferase (LCAT) is an enzyme that first hydrolyzes the sn-2 position of phospholipids, preferentially a diacylphosphocholine, and then transfers the fatty acid to cholesterol to yield a cholesteryl ester. HDL ApoA-I is the principal catalytic activator for LCAT. Activity of LCAT on nascent or lipid-poor HDL particles composed of phospholipid, cholesterol and ApoA-I allows the maturation of HDL particles into lipid-rich spherical particles that contain a core of cholesteryl ester surrounded by phospholipid and ApoA-I on the surface. This article reviews the recent progress in elucidating structural aspects of the interaction between LCAT and ApoA-I. In the last decade, there has been considerable progress in understanding the structure of ApoA-I and the central helices 5, 6, and 7 that are known to activate LCAT. However, much less information has been forthcoming describing the 3D structure and conformation of LCAT required to catalyze two separate reactions within a single monomeric peptide.
Sorci-Thomas
Mary G
MG
Department of Pathology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1016, USA, Tel.: +1 336 716 2147, , msthomas@wfubmc.edu.
Bhat
Shaila
S
Thomas
Michael J
MJ