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@ARTICLE{Gogonea:14185,
author = {Gogonea, V. and Wu, Z. and Lee, X. and Pipich, V. and Li,
X.-M. and Ioffe, A. and DiDonato, J.A. and Hazen, S.L.},
title = {{C}ongruency between biophysical data from multiple
platforms and molecular dynamics simulation of the double
super helix model of nascent high-density lipoprotein},
journal = {Biochemistry},
volume = {49},
issn = {0006-2960},
address = {Columbus, Ohio},
publisher = {American Chemical Society},
reportid = {PreJuSER-14185},
pages = {7323 - 7343},
year = {2010},
note = {This study was supported by National Institutes of Health
Grants P01 HL098055, P01 HL076491-055328, P01 HL087018-02001
and R01 DK 080732-01.},
abstract = {The predicted structure and molecular trajectories from >80
ns molecular dynamics simulation of the solvated
Double-Super Helix (DSH) model of nascent high-density
lipoprotein (HDL) were determined and compared with
experimental data on reconstituted nascent HDL obtained from
multiple biophysical platforms, including small angle
neutron scattering (SANS) with contrast variation,
hydrogen-deuterium exchange tandem mass spectrometry
(H/D-MS/MS), nuclear magnetic resonance spectroscopy (NMR),
cross-linking tandem mass spectrometry (MS/MS), fluorescence
resonance energy transfer (FRET), electron spin resonance
spectroscopy (ESR), and electron microscopy. In general,
biophysical constraints experimentally derived from the
multiple platforms agree with the same quantities evaluated
using the simulation trajectory. Notably, key structural
features postulated for the recent DSH model of nascent HDL
are retained during the simulation, including (1) the
superhelical conformation of the antiparallel apolipoprotein
A1 (apoA1) chains, (2) the lipid micellar-pseudolamellar
organization, and (3) the solvent-exposed Solar Flare loops,
proposed sites of interaction with LCAT (lecithin
cholesteryl acyltransferase). Analysis of salt bridge
persistence during simulation provides insights into
structural features of apoA1 that forms the backbone of the
lipoprotein. The combination of molecular dynamics
simulation and experimental data from a broad range of
biophysical platforms serves as a powerful approach to
studying large macromolecular assemblies such as
lipoproteins. This application to nascent HDL validates the
DSH model proposed earlier and suggests new structural
details of nascent HDL.},
keywords = {Apolipoprotein A-I: chemistry / Biophysics / Deuterium /
Hydrogen / Lipids / Lipoproteins: chemistry / Lipoproteins,
HDL: chemistry / Macromolecular Substances / Magnetic
Resonance Spectroscopy / Molecular Dynamics Simulation /
Phosphatidylcholine-Sterol O-Acyltransferase / Protein
Structure, Secondary / Apolipoprotein A-I (NLM Chemicals) /
Lipids (NLM Chemicals) / Lipoproteins (NLM Chemicals) /
Lipoproteins, HDL (NLM Chemicals) / Macromolecular
Substances (NLM Chemicals) / Hydrogen (NLM Chemicals) /
Deuterium (NLM Chemicals) / Phosphatidylcholine-Sterol
O-Acyltransferase (NLM Chemicals) / J (WoSType)},
cin = {IFF-4 / IFF-5 / Jülich Centre for Neutron Science JCNS
(JCNS) ; JCNS},
ddc = {570},
cid = {I:(DE-Juel1)VDB784 / I:(DE-Juel1)VDB785 /
I:(DE-Juel1)JCNS-20121112},
pnm = {BioSoft: Makromolekulare Systeme und biologische
Informationsverarbeitung / Großgeräte für die Forschung
mit Photonen, Neutronen und Ionen (PNI)},
pid = {G:(DE-Juel1)FUEK505 / G:(DE-Juel1)FUEK415},
experiment = {EXP:(DE-MLZ)KWS2-20140101},
shelfmark = {Biochemistry $\&$ Molecular Biology},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:20687589},
pmc = {pmc:PMC2940317},
UT = {WOS:000281052600010},
doi = {10.1021/bi100588a},
url = {https://juser.fz-juelich.de/record/14185},
}