Eur Biophys J (2009) 38:145–158 DOI 10.1007/s00249-008-0368-y 123 REVIEW Molecular structure of low density lipoprotein: current status and future challenges Ruth Prassl · Peter Laggner Received: 13 June 2008 / Accepted: 28 August 2008 / Published online: 17 September 2008  European Biophysical Societies' Association 2008 Abstract This review highlights recent advances in struc- tural studies on low density lipoprotein (LDL) with particu- lar emphasis on the apolipoprotein moiety of LDL, apolipoprotein B100 (apoB100). Various molecular aspects of LDL are outlined and obstacles to structure determina- tion are addressed. In this context, the prevailing concep- tions of the molecular assembly of LDL and how the synergy of complementary biochemical, biophysical and molecular simulation approaches has lead to the current structural model of LDL are discussed. Evidence is pre- sented that structural heterogeneity and the intrinsic dynamics of LDL are key determinants of the functionality of LDL in both health and disease. Some key research directions, remaining open questions and rapidly emerging new concepts for medical applications of LDL, are further- more outlined. The article concludes by providing an out- look concerning promising future strategies for the clariWcation of the molecular details of LDL, in particular of apoB100, combining recent advances in molecular mod- eling with developments of novel experimental techniques. Although new insights into the molecular organization of LDL are forthcoming, many open questions remain unanswered. The major challenge of the next decade will certainly be the elucidation of the molecular structural and dynamic features of apoB100. Keywords Low density lipoprotein · Apolipoprotein B100 · Molecular structure Abbreviations LDL Low density lipoprotein apoB100 Apolipoprotein B100 SAXS Small angle X-ray scattering SANS Small angle neutron scattering MRI Magnetic resonance imaging VLDL Very low density lipoprotein IDL Intermediate density lipoprotein Introduction Low density lipoprotein (LDL) is one of the most fascinat- ing macromolecular assemblies ever evolved by nature and has consequently attracted the attention of scientists for decades. As the principal transporter for cholesterol in the blood, circulating LDL guarantees a constant supply of cholesterol for tissues and cells and is an essential constituent of human life. The cellular uptake of LDL is mediated by speciWc receptors, either the classical B/E receptor or the scavenger receptor pathway (Brown and Goldstein 1976; Steinberg et al. 1989), and is strongly dependent on the structure of LDL particles and on the proper conformational orientation of apolipoprotein B100 (apoB100) located on the surface of LDL. The speciWc interactions of apoB100 with cellular receptors are the main focus of interest because these recognition mechanisms are intimately involved in the emergence and progression of various diseases, such as hypercholesterolemia, hyperlipidemia and atherogenesis. In particular, raised plasma levels of LDL are linked to an increased risk for the progression of atherosclerosis and car- diovascular diseases (Lusis 2000). Moreover, dysregulations of LDL due to abnormalities in LDL structure have been identiWed as independent predictors of risk for coronary heart diseases (Packard et al. 2000; Packard 2006). R. Prassl (&) · P. Laggner Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Schmiedlstr. 6, 8042 Graz, Austria e-mail: ruth.prassl@oeaw.ac.at