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Comprehensive Overview Of Biophysical Studies Of Lipoprotein Stability | 52843
Journal of Analytical & Bioanalytical Techniques
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Lipoproteins are nanoparticles comprised of proteins and lipids that provide vehicles for transport of fat and cholesterol in
circulation. High levels of certain lipoproteins increase the risk of heart disease. Each lipoprotein is a non-covalent assembly
of several proteins and several hundred lipids. The major challenge in the biophysical analysis of lipoproteins arises from their
heterogeneity in size (7-100 nm), density (1.06-1.22 g/L), and protein and lipid composition. Moreover, lipoproteins are highly
dynamic assemblies undergoing continuous remodeling via various enzymatic and non-enzymatic reactions. This provides a
major challenge for detailed structural studies of lipoproteins. To overcome this challenge, we designed an integrated biophysical
approach by combining far- and near-UV circular dichroism (CD) spectroscopy, turbidity, differential scanning calorimetry
(DSC), fluorescence spectroscopy, transmission electron microscopy (EM), size-exclusion chromatography (SEC) and other
methods to analyze the structure and remodeling of all major lipoprotein classes. This integrated approach was used to study
thermal denaturation of human low- and high-density lipoproteins (LDL and HDL, or bad and good cholesterol). The results
clearly showed that lipoprotein stability is controlled by kinetics barriers. Interestingly, heat-induced remodeling of all lipoproteins
involves partial protein unfolding/dissociation and lipoprotein fusion and rupture. These structural transitions mimic key aspects
of in vivo lipoprotein remodeling. These and other emerging approaches will allow one to study structural, dynamic and functional
properties of larger more challenging systems. Ultimately, such integrated approaches are hoped to bridge the gap between the
biophysical studies of isolated macromolecules or their complexes, and the complexity of cellular systems.
Shobini Jayaraman has completed her PhD from Indian Institute of Technology Madras, India and Post-doctoral studies from Weizmann Institute of Science, Israel. She was the recipient of Sir Charles Clore Fellowship at Weizmann Institute of Science. Currently, she is a Senior Research Scientist at Boston University School of Medicine. She serves as the liaison for academic and industrial contract research services at Boston University. She has published more than 25 papers in reputed journals. Her recent publication in JBC has been chosen as paper of the month in May-2014 by International Atherosclerosis Society.