1l6l: Difference between revisions
New page: left|200px<br /> <applet load="1l6l" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l6l, resolution 2.3Å" /> '''Structures of Apolip... |
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[[Image:1l6l.gif|left|200px]]<br /> | [[Image:1l6l.gif|left|200px]]<br /><applet load="1l6l" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1l6l, resolution 2.3Å" /> | caption="1l6l, resolution 2.3Å" /> | ||
'''Structures of Apolipoprotein A-II and a Lipid Surrogate Complex Provide Insights into Apolipoprotein-Lipid Interactions'''<br /> | '''Structures of Apolipoprotein A-II and a Lipid Surrogate Complex Provide Insights into Apolipoprotein-Lipid Interactions'''<br /> | ||
==Overview== | ==Overview== | ||
Apolipoproteins A-I and A-II form the major protein constituents of | Apolipoproteins A-I and A-II form the major protein constituents of high-density lipid particles (HDL), the concentration of which is inversely correlated with the frequency of heart disease in humans. Although the physiological role of apolipoprotein A-II is unclear, evidence for its involvement in free fatty acid metabolism in mice has recently been obtained. Currently, the best characterized activity of apolipoprotein A-II is its potent antagonism of the anti-atherogenic and anti-inflammatory activities of apolipoprotein A-I, probably due to its competition with the latter for lipid acyl side chains in HDL. Many interactions of apolipoprotein A-I with enzymes and proteins involved in reverse cholesterol transport and HDL maturation are mediated by lipid-bound protein. The structural bases of interaction with lipids are expected to be common to exchangeable apolipoproteins and attributable to amphipathic alpha-helices present in each of them. Thus, characterization of apolipoprotein-lipid interactions in any apolipoprotein is likely to provide information that is applicable to the entire class. We report structures of human apolipoprotein A-II and its complex with beta-octyl glucoside, a widely used lipid surrogate. The former shows that disulfide-linked dimers of apolipoprotein A-II form amphipathic alpha-helices which aggregate into tetramers. Dramatic changes, observed in the presence of beta-octyl glucoside, might provide clues to the structural basis for its antagonism of apolipoprotein A-I. Additionally, excursions of individual molecules of apolipoprotein A-II from a common helical architecture in both structures indicate that lipid-bound apolipoproteins are likely to have an ensemble of related conformations. These structures provide the first experimental paradigm for description of apolipoprotein-lipid interactions at the atomic level. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1L6L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with BOG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1L6L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=BOG:'>BOG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L6L OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Carson, M.]] | [[Category: Carson, M.]] | ||
[[Category: Hussain, M | [[Category: Hussain, M M.]] | ||
[[Category: Kumar, M | [[Category: Kumar, M S.]] | ||
[[Category: Murthy, H | [[Category: Murthy, H M.K.]] | ||
[[Category: BOG]] | [[Category: BOG]] | ||
[[Category: apolipoprotein]] | [[Category: apolipoprotein]] | ||
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[[Category: high density lipid]] | [[Category: high density lipid]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:41:52 2008'' | ||
Revision as of 14:41, 21 February 2008
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Structures of Apolipoprotein A-II and a Lipid Surrogate Complex Provide Insights into Apolipoprotein-Lipid Interactions
OverviewOverview
Apolipoproteins A-I and A-II form the major protein constituents of high-density lipid particles (HDL), the concentration of which is inversely correlated with the frequency of heart disease in humans. Although the physiological role of apolipoprotein A-II is unclear, evidence for its involvement in free fatty acid metabolism in mice has recently been obtained. Currently, the best characterized activity of apolipoprotein A-II is its potent antagonism of the anti-atherogenic and anti-inflammatory activities of apolipoprotein A-I, probably due to its competition with the latter for lipid acyl side chains in HDL. Many interactions of apolipoprotein A-I with enzymes and proteins involved in reverse cholesterol transport and HDL maturation are mediated by lipid-bound protein. The structural bases of interaction with lipids are expected to be common to exchangeable apolipoproteins and attributable to amphipathic alpha-helices present in each of them. Thus, characterization of apolipoprotein-lipid interactions in any apolipoprotein is likely to provide information that is applicable to the entire class. We report structures of human apolipoprotein A-II and its complex with beta-octyl glucoside, a widely used lipid surrogate. The former shows that disulfide-linked dimers of apolipoprotein A-II form amphipathic alpha-helices which aggregate into tetramers. Dramatic changes, observed in the presence of beta-octyl glucoside, might provide clues to the structural basis for its antagonism of apolipoprotein A-I. Additionally, excursions of individual molecules of apolipoprotein A-II from a common helical architecture in both structures indicate that lipid-bound apolipoproteins are likely to have an ensemble of related conformations. These structures provide the first experimental paradigm for description of apolipoprotein-lipid interactions at the atomic level.
DiseaseDisease
Known diseases associated with this structure: Apolipoprotein A-II deficiency OMIM:[107670], Hypercholesterolemia, familial, modification of OMIM:[107670]
About this StructureAbout this Structure
1L6L is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structures of apolipoprotein A-II and a lipid-surrogate complex provide insights into apolipoprotein-lipid interactions., Kumar MS, Carson M, Hussain MM, Murthy HM, Biochemistry. 2002 Oct 1;41(39):11681-91. PMID:12269810
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