Volumetric determination of apolipoprotein stoichiometry of circulating HDL subspecies1[S]
Although HDL is inversely correlated with coronary heart disease, elevated HDL-cholesterol is not always protective. Additionally, HDL has biological functions that transcend any antiatherogenic role: shotgun proteomics show that HDL particles contain 84 proteins (latest count), many correlating wit...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-10-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520352998 |
| _version_ | 1819077014872653824 |
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| author | Jere P. Segrest Marian C. Cheung Martin K. Jones |
| author_facet | Jere P. Segrest Marian C. Cheung Martin K. Jones |
| author_sort | Jere P. Segrest |
| collection | DOAJ |
| description | Although HDL is inversely correlated with coronary heart disease, elevated HDL-cholesterol is not always protective. Additionally, HDL has biological functions that transcend any antiatherogenic role: shotgun proteomics show that HDL particles contain 84 proteins (latest count), many correlating with antioxidant and anti-inflammatory properties of HDL. ApoA-I has been suggested to serve as a platform for the assembly of these protein components on HDL with specific functions - the HDL proteome. However, the stoichiometry of apoA-I in HDL subspecies is poorly understood. Here we use a combination of immunoaffinity chromatography data and volumetric analysis to evaluate the size and stoichiometry of LpA-I and LpA-I,A-II particles. We conclude that there are three major LpA-I subspecies: two major particles, HDL[4] in the HDL3 size range (d = 85.0 ± 1.2 å) and HDL[7] in the HDL2 size range (d = 108.5 ± 3.8 å) with apoA-I stoichiometries of 3 and 4, respectively, and a small minor particle, HDL[1] (d = 73.8 ± 2.1å) with an apoA-I stoichiometry of 2. Additionally, we conclude that the molar ratio of apolipoprotein to surface lipid is significantly higher in circulating HDL subspecies than in reconstituted spherical HDL particles, presumably reflecting a lack of phospholipid transfer protein in reconstitution protocols. |
| first_indexed | 2024-12-21T18:50:28Z |
| format | Article |
| id | doaj.art-6daa8b01785945a88ce8e2a58fba86d8 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-21T18:50:28Z |
| publishDate | 2013-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-6daa8b01785945a88ce8e2a58fba86d82022-12-21T18:53:47ZengElsevierJournal of Lipid Research0022-22752013-10-01541027332744Volumetric determination of apolipoprotein stoichiometry of circulating HDL subspecies1[S]Jere P. Segrest0Marian C. Cheung1Martin K. Jones2To whom correspondence should be addressed; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294; and; Center for Computational and Structural Dynamics, University of Alabama at Birmingham, Birmingham, AL 35294; andDepartment of Medicine, University of Washington, Seattle, WA 98195Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294; and; Center for Computational and Structural Dynamics, University of Alabama at Birmingham, Birmingham, AL 35294; andAlthough HDL is inversely correlated with coronary heart disease, elevated HDL-cholesterol is not always protective. Additionally, HDL has biological functions that transcend any antiatherogenic role: shotgun proteomics show that HDL particles contain 84 proteins (latest count), many correlating with antioxidant and anti-inflammatory properties of HDL. ApoA-I has been suggested to serve as a platform for the assembly of these protein components on HDL with specific functions - the HDL proteome. However, the stoichiometry of apoA-I in HDL subspecies is poorly understood. Here we use a combination of immunoaffinity chromatography data and volumetric analysis to evaluate the size and stoichiometry of LpA-I and LpA-I,A-II particles. We conclude that there are three major LpA-I subspecies: two major particles, HDL[4] in the HDL3 size range (d = 85.0 ± 1.2 å) and HDL[7] in the HDL2 size range (d = 108.5 ± 3.8 å) with apoA-I stoichiometries of 3 and 4, respectively, and a small minor particle, HDL[1] (d = 73.8 ± 2.1å) with an apoA-I stoichiometry of 2. Additionally, we conclude that the molar ratio of apolipoprotein to surface lipid is significantly higher in circulating HDL subspecies than in reconstituted spherical HDL particles, presumably reflecting a lack of phospholipid transfer protein in reconstitution protocols.http://www.sciencedirect.com/science/article/pii/S0022227520352998apolipoprotein A-Iapolipoprotein A-IILpA-ILpA-I,A-IIHDL platformHDL surface monolayer |
| spellingShingle | Jere P. Segrest Marian C. Cheung Martin K. Jones Volumetric determination of apolipoprotein stoichiometry of circulating HDL subspecies1[S] Journal of Lipid Research apolipoprotein A-I apolipoprotein A-II LpA-I LpA-I,A-II HDL platform HDL surface monolayer |
| title | Volumetric determination of apolipoprotein stoichiometry of circulating HDL subspecies1[S] |
| title_full | Volumetric determination of apolipoprotein stoichiometry of circulating HDL subspecies1[S] |
| title_fullStr | Volumetric determination of apolipoprotein stoichiometry of circulating HDL subspecies1[S] |
| title_full_unstemmed | Volumetric determination of apolipoprotein stoichiometry of circulating HDL subspecies1[S] |
| title_short | Volumetric determination of apolipoprotein stoichiometry of circulating HDL subspecies1[S] |
| title_sort | volumetric determination of apolipoprotein stoichiometry of circulating hdl subspecies1 s |
| topic | apolipoprotein A-I apolipoprotein A-II LpA-I LpA-I,A-II HDL platform HDL surface monolayer |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520352998 |
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