Our research focus is on protein folding, structure and stability. It includes the analysis of the energetic-structure-function relationship and folding pathways in proteins and peptides by circular dichroism spectroscopy, differential scanning calorimetry, fluorescence, x-ray crystallography, and site-directed mutagenesis.
Our on-going NIH-funded work is aimed at understanding the energetic and structural basis for the conformational plasticity of apolipoproteins. These are protein constituents of lipoproteins that mediate lipid transport and metabolism and are central in the pathogenesis of atherosclerosis, stroke, and certain forms of amyloidosis. Apolipoproteins are distinct in their structural adaptability to various lipoprotein particles and to plasma. We try to understand in molecular detail the energetic and structural basis for this adaptability.
A major focus of our research is on the molecular mechanisms of lipoprotein stabilization and fusion. In 2002 we revealed that lipoprotein stability is determined by kinetic barriers. Similar barriers may modulate in-vivo lipoprotein transformations. Our goal is to obtain key molecular determinants for these energy barriers.
- Member, Amyloidosis Center, Boston University
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Graduate Medical Sciences
- Brandeis University, PhD
- Moscow State University, MS
- Published on 10/19/2021
Peterle D, Klimtchuk ES, Wales TE, Georgescauld F, Connors LH, Engen JR, Gursky O. A Conservative Point Mutation in a Dynamic Antigen-binding Loop of Human Immunoglobulin ?6 Light Chain Promotes Pathologic Amyloid Formation. J Mol Biol. 2021 12 03; 433(24):167310. PMID: 34678302.
- Published on 10/14/2021
Lewkowicz E, Gursky O. Dynamic protein structures in normal function and pathologic misfolding in systemic amyloidosis. Biophys Chem. 2022 01; 280:106699. PMID: 34773861.
- Published on 10/2/2021
Jayaraman S, Pérez A, Miñambres I, Sánchez-Quesada JL, Gursky O. Heparin binding triggers human VLDL remodeling by circulating lipoprotein lipase: Relevance to VLDL functionality in health and disease. Biochim Biophys Acta Mol Cell Biol Lipids. 2022 01; 1867(1):159064. PMID: 34610468.
- Published on 6/28/2021
Lewkowicz E, Jayaraman S, Gursky O. Protein Amyloid Cofactors: Charged Side-Chain Arrays Meet Their Match? Trends Biochem Sci. 2021 08; 46(8):626-629. PMID: 34210544.
- Published on 9/24/2020
Gursky O. Structural Basis for Vital Function and Malfunction of Serum Amyloid A: an Acute-Phase Protein that Wears Hydrophobicity on Its Sleeve. Curr Atheroscler Rep. 2020 09 24; 22(11):69. PMID: 32968930.
- Published on 7/1/2020
Gursky O. Novel clinical manifestations and treatment of hereditary apoA-I amyloidosis: when a good protein turns bad. Kidney Int. 2020 07; 98(1):62-64. PMID: 32571494.
- Published on 4/11/2020
Jayaraman S, Chavez OR, Pérez A, Miñambres I, Sánchez-Quesada JL, Gursky O. Binding to heparin triggers deleterious structural and biochemical changes in human low-density lipoprotein, which are amplified in hyperglycemia. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 08; 1865(8):158712. PMID: 32289504.
- Published on 2/6/2020
Frame NM, Kumanan M, Wales TE, Bandara A, Fändrich M, Straub JE, Engen JR, Gursky O. Structural Basis for Lipid Binding and Function by an Evolutionarily Conserved Protein, Serum Amyloid A. J Mol Biol. 2020 03 27; 432(7):1978-1995. PMID: 32035904.
- Published on 5/21/2019
Jayaraman S, Fändrich M, Gursky O. Synergy between serum amyloid A and secretory phospholipase A2. Elife. 2019 05 21; 8. PMID: 31111824.
- Published on 3/5/2019
Jayaraman S, Baveghems C, Chavez OR, Rivas-Urbina A, Sánchez-Quesada JL, Gursky O. Effects of triacylglycerol on the structural remodeling of human plasma very low- and low-density lipoproteins. Biochim Biophys Acta Mol Cell Biol Lipids. 2019 07; 1864(7):1061-1071. PMID: 30844432.
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