2ou1
From Proteopedia
(New page: 200px<br /> <applet load="2ou1" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ou1, resolution 2.0Å" /> '''Structures of apolip...) |
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| - | [[Image:2ou1.gif|left|200px]]<br /> | + | [[Image:2ou1.gif|left|200px]]<br /><applet load="2ou1" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2ou1" size=" | + | |
caption="2ou1, resolution 2.0Å" /> | caption="2ou1, resolution 2.0Å" /> | ||
'''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== | ||
| - | 2OU1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure | + | 2OU1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry 1L6K. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OU1 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Carson, M | + | [[Category: Carson, M C.]] |
| - | [[Category: Hussain, M | + | [[Category: Hussain, M M.]] |
| - | [[Category: Kumar, M | + | [[Category: Kumar, M S.]] |
| - | [[Category: Murthy, H | + | [[Category: Murthy, H M.K.]] |
[[Category: apolipoprotein]] | [[Category: apolipoprotein]] | ||
[[Category: apolipoprotein a-ii]] | [[Category: apolipoprotein a-ii]] | ||
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[[Category: high density lipoproteins]] | [[Category: high density lipoproteins]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:22:27 2008'' |
Revision as of 16:22, 21 February 2008
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Structures of apolipoprotein A-II and a lipid surrogate complex provide insights into apolipoprotein-lipid interactions
Contents |
Overview
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
Known diseases associated with this structure: Apolipoprotein A-II deficiency OMIM:[107670], Hypercholesterolemia, familial, modification of OMIM:[107670]
About this Structure
2OU1 is a Single protein structure of sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1L6K. Full crystallographic information is available from OCA.
Reference
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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