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@ARTICLE{Gogonea:187412,
author = {Gogonea, V. and Gerstenecker, G. S. and Gerstenecker, G. S.
and Wu, Z. and Lee, X. and Topbas, C. and Wagner, M. A. and
Tallant, T. C. and Smith, J. D. and Callow, P. and Pipich,
V. and Malet, H. and Schoehn, G. and DiDonato, J. A. and
Hazen, S. L.},
title = {{T}he low-resolution structure of n{HDL} reconstituted with
{DMPC} with and without cholesterol reveals a mechanism for
particle expansion},
journal = {Journal of lipid research},
volume = {54},
number = {4},
issn = {0022-2275},
address = {Bethesda, Md.},
publisher = {ASBMB},
reportid = {PreJuSER-187412},
pages = {966 - 983},
year = {2013},
note = {Record converted 2014-10-14 05:10:08},
abstract = {Small-angle neutron scattering (SANS) with contrast
variation was used to obtain the low-resolution structure of
nascent HDL (nHDL) reconstituted with dimyristoyl
phosphatidylcholine (DMPC) in the absence and presence of
cholesterol, [apoA1:DMPC (1:80, mol:mol) and
apoA1:DMPC:cholesterol (1:86:9, mol:mol:mol)]. The overall
shape of both particles is discoidal with the low-resolution
structure of apoA1 visualized as an open, contorted, and out
of plane conformation with three arms in nascent
HDL/dimyristoyl phosphatidylcholine without cholesterol
(nHDL(DMPC)) and two arms in nascent HDL/dimyristoyl
phosphatidylcholine with cholesterol (nHDL(DMPC+Chol)). The
low-resolution shape of the lipid phase in both nHDL(DMPC)
and nHDL(DMPC+Chol) were oblate ellipsoids, and fit well
within their respective protein shapes. Modeling studies
indicate that apoA1 is folded onto itself in nHDL(DMPC),
making a large hairpin, which was also confirmed
independently by both cross-linking mass spectrometry and
hydrogen-deuterium exchange (HDX) mass spectrometry
analyses. In nHDL(DMPC+Chol), the lipid was expanded and no
hairpin was visible. Importantly, despite the overall
discoidal shape of the whole particle in both nHDL(DMPC) and
nHDL(DMPC+Chol), an open conformation (i.e., not a closed
belt) of apoA1 is observed. Collectively, these data show
that full length apoA1 retains an open architecture that is
dictated by its lipid cargo. The lipid is likely
predominantly organized as a bilayer with a micelle domain
between the open apoA1 arms. The apoA1 configuration
observed suggests a mechanism for accommodating changing
lipid cargo by quantized expansion of hairpin structures.},
keywords = {Apolipoprotein A-I: chemistry / Cholesterol: chemistry /
Dimyristoylphosphatidylcholine: chemistry / High-Density
Lipoproteins, Pre-beta: chemistry / Humans / Mass
Spectrometry / Scattering, Small Angle / Apolipoprotein A-I
(NLM Chemicals) / High-Density Lipoproteins, Pre-beta (NLM
Chemicals) / Cholesterol (NLM Chemicals) /
Dimyristoylphosphatidylcholine (NLM Chemicals)},
cin = {KWS1},
ddc = {540},
cid = {I:(DE-MLZ)4128},
pnm = {54G - JCNS (POF2-54G24)},
pid = {G:(DE-HGF)POF2-54G24},
experiment = {EXP:(DE-MLZ)KWS1-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:23349207},
pmc = {pmc:PMC3606002},
UT = {WOS:000316462600011},
doi = {10.1194/jlr.M032763},
url = {https://juser.fz-juelich.de/record/187412},
}