Changes in helical content or net charge of apolipoprotein C-I alter its affinity for lipid/water interfaces

Meyers, Nathan L.; Wang, Libo; Gursky, Olga; Small, Donald

doi:10.1194/jlr.m037531

Cited by 11 publications

(26 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 for LPL regulation by apoC-III. For comparison, this model includes the other apoCs, apoC-I and apoC-II, which we characterized in previous studies (45,46). ApoC-II, the required cofactor of Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Our laboratory has used envelope pressure ( ENV ) to refer to retention pressure (i.e., the highest pressure at which a peptide is retained at an interface before being ejected) (46,53).…”

Section: Compression and Expansion Of Lipid/water Interfacesmentioning

confidence: 99%

“…The oil-drop tensiometer measures the surface tension of lipid/ water interfaces, which is high at hydrophobic surfaces (40,41,43). Peptide adsorption to these interfaces decreases surface tension, and the magnitude of this change reflects the peptide's ability to remodel the surface (41,(44)(45)(46). After peptide adsorption, expansion and compression of the interface mimic local tension changes, such as those induced by LPL activity, and reveal tension values at which peptide desorbs (44)(45)(46).…”

mentioning

confidence: 99%

“…Peptide adsorption to these interfaces decreases surface tension, and the magnitude of this change reflects the peptide's ability to remodel the surface (41,(44)(45)(46). After peptide adsorption, expansion and compression of the interface mimic local tension changes, such as those induced by LPL activity, and reveal tension values at which peptide desorbs (44)(45)(46). By applying this methodology to apoC-III variants, we characterized the quantitative effects of individual mutations on the ability of apoC-III to remodel and remain bound to surfaces mimicking TG-lipoproteins.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Aromatic residues in the C terminus of apolipoprotein C-III mediate lipid binding and LPL inhibition

Meyers

Larsson

Vorrsjö

et al. 2017

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org triglyceride (TG)-rich lipoproteins (i.e., VLDLs and chylomicrons) (2-4). In normolipidemic individuals, plasma concentrations of apoC-III are 80-100 g/ml, with approximately 60% of apoC-III associated with HDL, 20% with LDL, 20% with the TG-rich lipoproteins, and very little free in plasma (5). In the hypertriglyceridemic state, plasma apoC3 levels increase to >300 g/ml, and the percentage on TG-rich lipoproteins increases from 20% to upward of 60% (5-7). In fact, animal and human studies have established a strong, positive correlation between elevated plasma apoC-III levels and TG levels, which are an independent risk factor for atherosclerotic CVD (1, 8). The overexpression of human apoC-III in mice promoted the development of atherosclerosis and was associated with elevated TG levels, but low HDL cholesterol levels, in plasma (9). In contrast, targeted disruption of apoC-III in mice was associated with the rapid catabolism of TG-rich lipoproteins and a 70% decrease in fasting TG levels (10).Beyond these mouse models, clinical studies established the importance of apoC-III as a predictor of CVD outcomes. Increased serum apoC-III levels were associated with elevated serum TG and, in turn, insulin resistance, CVD, and type II diabetes (11-13). Plasma levels of apoC-III independently predicted risk for coronary heart disease, even after control for blood lipids (12,14). Further indicating a crucial role of apoC-III in regulating lipid metabolism, subjects with gain-of-function mutations in the apoC-III gene exhibited hypertriglyceridemia that was associated with elevated plasma apoC-III protein levels (15, 16). In contrast, subjects with loss-of-function mutations in the apoC-III gene exhibited reduced TG and apoC-III levels (17-21), which had a cardioprotective effect. apoC-III is a small (79 amino acid), O-glycosylated, secretory protein that is synthesized in the liver and intestine (1). ApoC-III is the most abundant apoC in humans and circulates in plasma as a component of HDLs and the Abstract

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Compression and Expansion Of Lipid/water Interfacesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Aromatic residues in the C terminus of apolipoprotein C-III mediate lipid binding and LPL inhibition

Meyers

Larsson

Vorrsjö

et al. 2017

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…We have been using a novel surface chemistry technique, oil-drop tensiometry, to study the pressure-mediated adsorption, desorption, and fl exibility behavior of apolipoproteins, their segments, and consensus peptides at physiologically relevant model lipoprotein surfaces ( 38,(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62), such as triolein/water (TO/W) and phosphatidylcholine/triolein/water (POPC/TO/W) interfaces. Our novel technique provides a unique point of view to look at the interaction between apolipoproteins and lipids.…”

mentioning

confidence: 99%

Surface behavior of apolipoprotein A-I and its deletion mutants at model lipoprotein interfaces

Wang

Mei

Atkinson

et al. 2014

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org properties of apoA-I arise primarily through its important roles in the pathway of reverse cholesterol transport; where apoA-I stabilizes and maintains the structure of HDL particles, promotes cellular cholesterol effl ux by binding to specifi c ATP binding cassette transporters, interacts with the enzyme lecithin:cholesterol acyltransferase (LCAT) to drive the maturation of HDL particles, binds and modifi es the lipoprotein surface to facilitate enzyme reactions, and interacts with the scavenger receptor class B type 1 for selective cholesterol ester (CE) uptake by the liver for excretion ( 2-4 ).ApoA-I exists in lipid-free, lipid-poor, and lipid-bound states in plasma, and exchanges among HDL and TAGrich lipoprotein particles like very low density lipoproteins (VLDLs) and chylomicrons (CMs) ( 5 ). ApoA-I interacts primarily with the hydrocarbon chains of the phospholipids (PL) on discoidal and spherical HDLs ( 6-8 ) and may also interact with the hydrophobic CE core of spherical HDL and the hydrophobic TAG core of TAG-rich lipoproteins. The conformational fl exibility of apoA-I allows it to adopt a variety of conformations involving lipid adsorption, partial or full desorption, and fl exible unfolding and refolding in diverse physical environments to facilitate its multiple functions. Studies of the molecular mechanisms of the lipid association and the conformational fl exibility of apoA-I are essential for understanding the structure-function relationships.ApoA-I has an exon 3 encoded region (residues 1-43), and an exon 4 encoded region (residues 44-243) that contains 10 11/22-mer tandem repeat amino acid segments that are predicted to form class A and class Y amphipathic ␣ -helices (A ␣ Hs) ( 9, 10 ). These A ␣ Hs (helix 1-10) are the lipid binding motif of apoA-I and the structural basis for its multiple functions. Segment deletion and point mutation studies have elucidated the possible conformation and functions for each helical segment (11)(12)(13)(14)(15)(16) Apolipoprotein A-I (apoA-I) is a major protein of high density lipoproteins (HDLs) and is also present on large triacylglycerol (TAG)-rich lipoproteins. Reduced plasma levels of HDL and apoA-I are the key risk factors for atherosclerosis and cardiovascular disease ( 1 ). The anti-atherogenic

show abstract

Proteogenomic review of the changes in primate apoC-I during evolution

Puppione

Whitelegge

2013

Front. Biol.

View full text Add to dashboard Cite

Apolipoprotein C-I has evolved more rapidly than any of the other soluble apolipoproteins. During the course of primate evolution, the gene for this apolipoprotein was duplicated. Prompted by our observation that the two resulting genes encode two distinct forms of apoC-I in great apes, we have reviewed both the genomic and proteomic data to examine what changes have occurred during the course of primate evolution. We have found data showing that one of the duplicated genes, known to be a pseudogene in humans, was also a pseudogene in Denisovans and Neandertals. Using genomic and proteomic data for primates, we will provide in this review evidence that the duplication took place after the divergence of New World monkeys from the human lineage and that the formation of the pseudogene took place after the divergence of the bonobos and chimpanzees from the human lineage.

show abstract

Changes in helical content or net charge of apolipoprotein C-I alter its affinity for lipid/water interfaces

Cited by 11 publications

References 60 publications

Aromatic residues in the C terminus of apolipoprotein C-III mediate lipid binding and LPL inhibition

Aromatic residues in the C terminus of apolipoprotein C-III mediate lipid binding and LPL inhibition

Surface behavior of apolipoprotein A-I and its deletion mutants at model lipoprotein interfaces

Proteogenomic review of the changes in primate apoC-I during evolution

Contact Info

Product

Resources

About