REEVALUATION OF THE STRUCTURE OF LOW-DENSITY LIPOPROTEINS

Low density lipoprotein (LDL) is,an established atherogenic factor. Mu ch effort has therefore been devoted to elucidation of its structure, yielding the generally accepted model according to which the neutral l ipids (cholesterol ester and triglycerides) form a lipid core emulsifi ed by phospholipids, cholesterol and the amphipathic Apolipoprotein B. Yet, the detailed structure of LDL is not clear. The present work was carried out with the aim of re-evaluating the LDL structure using the minimal number of assumptions: in view of the previously noted surfac e deficit (lack of sufficient PL and cholesterol to cover the surface of the lipidic core) we have assumed that polar head groups are not co vered by apo B. Other than that, we have 'allowed' Apo B to penetrate into the PL monolayers and the lipidic core and to pertrude into the s olution (be elevated above the PL head group level). We have also 'all owed' neutral lipid penetration into the monolayer and variation of th e thickness of the phospholipid monolayers within reasonable boundarie s. Based on the established values of relevant constants (molecular we ights and volumes, densities and surface areas) we have computed the r adius of the particle, the penetration of Apo B into lipidic milieus a nd the fraction of the surface area covered by Apo B as functions of t he LDL composition, the monolayer thickness and the 'elevation' of Apo B above this monolayer. These computations show that at least 40% of the LDL surface must be covered by protein and that the protein penetr ates, on the average, only about a half of the PL monolayer. Thus it i s not very likely to penetrate into the lipidic core. These general fe atures are preserved in the smaller LDL particles of hypertriglyceride mic patients. Assuming that no PL head group is covered by Apo B, the previously described immobilization of 20% of the phospholipids is lik ely to result from the interaction of Apo B with neighboring FL. Accor ding to our computations this can be regarded consistent with the prev iously proposed arrangement of the apo B as a '3-4 domain structure' o r a long string configuration but inconsistent with 'one domain' or 't wenty domain' structures.