Evidence map›Paper›PMID 19860440›Full record

ArticleBiochemistry2009

Dynamics of activation of lecithin:cholesterol acyltransferase by apolipoprotein A-I.

Martin K Jones, Andrea Catte, Ling Li, Jere P Segrest

Abstract read
In one paragraph

Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
6.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 51 citations in OpenAlex.

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  7. Molecular dynamics simulations of lipid nanodiscs.Biochimica et biophysica acta. Biomembranes · 2018
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Martin K JonesDepartment of Medicine and Atherosclerosis Research Unit, University ofAlabama, Birmingham, Alabama 35294, USA.
Andrea Catte
Ling Li
Jere P Segrest
University of Alabama · US

Funding

SYNTHETIC PEPTIDE STUDIES OF THE AMPHIPATHIC HELIXP01HL034343 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SEGREST, JERE P · 1985 to 2012
$18.8M
NHLBI NIH HHS P01 HL034343NHLBI NIH HHS P01 HL-34343
6 · The paper itself

Abstract

The product of transesterification of phospholipid acyl chains and unesterified cholesterol (UC) by the enzyme lecithin:cholesterol acyltransferase (LCAT) is cholesteryl ester (CE). Activation of LCAT by apolipoprotein (apo) A-I on nascent (discoidal) high-density lipoproteins (HDL) is essential for formation of mature (spheroidal) HDL during the antiatherogenic process of reverse cholesterol transport. Here we report all-atom and coarse-grained (CG) molecular dynamics (MD) simulations of HDL particles that have major implications for mechanisms of LCAT activation. Both the all-atom and CG simulations provide support for a model in which the helix 5/5 domains of apoA-I create an amphipathic "presentation tunnel" that exposes methyl ends of acyl chains at the bilayer center to solvent. Further, CG simulations show that UC also becomes inserted with high efficiency into the amphipathic presentation tunnel with its hydroxyl moiety (UC-OH) exposed to solvent; these results are consistent with trajectory analyses of the all-atom simulations showing that UC is being concentrated in the vicinity of the presentation tunnel. Finally, consistent with known product inhibition of CE-rich HDL by CE, CG simulations of CE-rich spheroidal HDL indicate partial blockage of the amphipathic presentation tunnel by CE. These results lead us to propose the following working hypothesis. After attachment of LCAT to discoidal HDL, the helix 5/5 domains in apoA-I form amphipathic presentation tunnels for migration of hydrophobic acyl chains and amphipathic UC from the bilayer to the phospholipase A2-like and esterification active sites of LCAT, respectively. This hypothesis is currently being tested by site-directed mutagenesis.

Indexed as

Apolipoprotein A-ICatalytic DomainCholesterolCholesterol EstersComputer SimulationEnzyme ActivationEsterificationHydrophobic and Hydrophilic InteractionsLipid BilayersLipoproteins, HDLModels, MolecularPhosphatidylcholine-Sterol O-AcyltransferaseProtein BindingProtein Structure, SecondaryApolipoprotein A-ICholesterolCholesterol EstersLipid BilayersLipoproteins, HDLPhosphatidylcholine-Sterol O-Acyltransferase

Identifiers

PMID19860440
PMCPMC2814595
OpenAlexW1972114344

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.