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Protein Backbone and Average Particle Dynamics in Reconstituted Discoidal and Spherical HDL Probed by Hydrogen Deuterium Exchange and Elastic Incoherent Neutron Scattering

1
Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
2
Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA
3
Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA
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Institut Laue Langevin, 71 avenue des Martyrs, CS 20156, F-38042 Grenoble CEDEX 9, France
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Université Joseph Fourier Grenoble I, UFR PhITEM, F-38041 Grenoble CEDEX 9, France
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Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Sydney, Sydney NSW 2052, Australia
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Institut Charles Sadron, CNRS-Université de Strasbourg, 23 rue du Loess, B.P. 84047, 67034 Strasbourg CEDEX 2, France
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Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 121; https://doi.org/10.3390/biom10010121 (registering DOI)
Received: 10 December 2019 / Revised: 29 December 2019 / Accepted: 6 January 2020 / Published: 10 January 2020
Lipoproteins are supramolecular assemblies of proteins and lipids with dynamic characteristics critically linked to their biological functions as plasma lipid transporters and lipid exchangers. Among them, spherical high-density lipoproteins are the most abundant forms of high-density lipoprotein (HDL) in human plasma, active participants in reverse cholesterol transport, and associated with reduced development of atherosclerosis. Here, we employed elastic incoherent neutron scattering (EINS) and hydrogen-deuterium exchange mass spectrometry (HDX-MS) to determine the average particle dynamics and protein backbone local mobility of physiologically competent discoidal and spherical HDL particles reconstituted with human apolipoprotein A-I (apoA-I). Our EINS measurements indicated that discoidal HDL was more dynamic than spherical HDL at ambient temperatures, in agreement with their lipid-protein composition. Combining small-angle neutron scattering (SANS) with contrast variation and MS cross-linking, we showed earlier that the most likely organization of the three apolipoprotein A-I (apoA-I) chains in spherical HDL is a combination of a hairpin monomer and a helical antiparallel dimer. Here, we corroborated those findings with kinetic studies, employing hydrogen-deuterium exchange mass spectrometry (HDX-MS). Many overlapping apoA-I digested peptides exhibited bimodal HDX kinetics behavior, suggesting that apoA-I regions with the same amino acid composition located on different apoA-I chains had different conformations and/or interaction environments. View Full-Text
Keywords: apolipoprotein A-I; high-density lipoprotein; chemical cross-linking; MS cross-linking; hydrogen-deuterium exchange mass spectrometry; elastic incoherent neutron scattering; thermal neutron; lipoprotein dynamics; lipoprotein softness; protein backbone dynamics apolipoprotein A-I; high-density lipoprotein; chemical cross-linking; MS cross-linking; hydrogen-deuterium exchange mass spectrometry; elastic incoherent neutron scattering; thermal neutron; lipoprotein dynamics; lipoprotein softness; protein backbone dynamics
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Gogonea, V.; Peters, J.; Gerstenecker, G.S.; Topbas, C.; Hou, L.; Combet, J.; DiDonato, J.A.; Smith, J.D.; Rye, K.-A.; Hazen, S.L. Protein Backbone and Average Particle Dynamics in Reconstituted Discoidal and Spherical HDL Probed by Hydrogen Deuterium Exchange and Elastic Incoherent Neutron Scattering. Biomolecules 2020, 10, 121.

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