Protein backbone and average particle dynamics in reconstituted discoidal and spherical HDL probed by hydrogen deuterium exchange and elastic incoherent neutron scattering

Valentin Gogonea, Judith Peters, Gary S. Gerstenecker, Celalettin Topbas, Liming Hou, Jérôme Combet, Joseph A. DiDonato, Kerry-Anne Rye, Stanley L. Hazen

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Abstract

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.
Original languageEnglish
Article number121
Pages (from-to)1-24
Number of pages24
JournalBiomolecules
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 2020
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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

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