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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.

Authors :
Gogonea, Valentin
Peters, Judith
Gerstenecker, Gary S.
Topbas, Celalettin
Liming Hou
Combet, Jérôme
DiDonato, Joseph A.
Smith, Jonathan D.
Rye, Kerry-Anne
Hazen, Stanley L.
Source :
Biomolecules (2218-273X). Jan2020, Vol. 10 Issue 1, p1-24. 39p.
Publication Year :
2020

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
2218273X
Volume :
10
Issue :
1
Database :
Academic Search Index
Journal :
Biomolecules (2218-273X)
Publication Type :
Academic Journal
Accession number :
141559993
Full Text :
https://doi.org/10.3390/biom10010121