|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
7
|
|
pubmed:dateCreated |
2010-2-8
|
|
pubmed:abstractText |
Conversion of discoidal phospholipid (PL)-rich high density lipoprotein (HDL) to spheroidal cholesteryl ester-rich HDL is a central step in reverse cholesterol transport. A detailed understanding of this process and the atheroprotective role of apolipoprotein A-I (apoA-I) requires knowledge of the structure and dynamics of these various particles. This study, combining computation with experimentation, illuminates structural features of apoA-I allowing it to incorporate varying amounts of PL. Molecular dynamics simulated annealing of PL-rich HDL models containing unesterified cholesterol results in double belt structures with the same general saddle-shaped conformation of both our previous molecular dynamics simulations at 310 K and the x-ray structure of lipid-free apoA-I. Conversion from a discoidal to a saddle-shaped particle involves loss of helicity and formation of loops in opposing antiparallel parts of the double belt. During surface expansion caused by the temperature-jump step, the curved palmitoyloleoylphosphatidylcholine bilayer surfaces approach planarity. Relaxation back into saddle-shaped structures after cool down and equilibration further supports the saddle-shaped particle model. Our kinetic analyses of reconstituted particles demonstrate that PL-rich particles exist in discrete sizes corresponding to local energetic minima. Agreement of experimental and computational determinations of particle size/shape and apoA-I helicity provide additional support for the saddle-shaped particle model. Truncation experiments combined with simulations suggest that the N-terminal proline-rich domain of apoA-I influences the stability of PL-rich HDL particles. We propose that apoA-I incorporates increasing PL in the form of minimal surface bilayers through the incremental unwinding of an initially twisted saddle-shaped apoA-I double belt structure.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-10542194,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-10787171,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-10956648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-11557764,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-12460572,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-12724319,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-14609337,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-15362856,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-15491614,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-15738977,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-15972827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-16418537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-16497665,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-16566598,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-16581834,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-16698792,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-17526499,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-17563120,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-17676061,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-18065479,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-19167289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-19610670,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-19812036,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-2125044,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-3107616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-3724523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-4368333,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-6273421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-6421314,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-7529585,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-7626742,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-7744765,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-7919584,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-8744570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-8749014,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-8749853,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-8845749,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-8942981,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-9003180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-9054424,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-9144081,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-9144767,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-9211897,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-9390287,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19948731-9665740
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
1083-351X
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
12
|
|
pubmed:volume |
285
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
4652-65
|
|
pubmed:dateRevised |
2011-7-25
|
|
pubmed:meshHeading |
pubmed-meshheading:19948731-Apolipoprotein A-I,
pubmed-meshheading:19948731-Circular Dichroism,
pubmed-meshheading:19948731-Computational Biology,
pubmed-meshheading:19948731-Humans,
pubmed-meshheading:19948731-Lipoproteins,
pubmed-meshheading:19948731-Lipoproteins, HDL,
pubmed-meshheading:19948731-Magnetic Resonance Spectroscopy,
pubmed-meshheading:19948731-Models, Molecular,
pubmed-meshheading:19948731-Molecular Dynamics Simulation,
pubmed-meshheading:19948731-Mutation,
pubmed-meshheading:19948731-Phosphatidylcholines
|
|
pubmed:year |
2010
|
|
pubmed:articleTitle |
Structures of discoidal high density lipoproteins: a combined computational-experimental approach.
|
|
pubmed:affiliation |
Department of Medicine and Atherosclerosis Research Unit, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
|
