2a01
From Proteopedia
(New page: 200px<br /> <applet load="2a01" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a01, resolution 2.40Å" /> '''Crystal Structure o...) |
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| - | [[Image:2a01.gif|left|200px]]<br /> | + | [[Image:2a01.gif|left|200px]]<br /><applet load="2a01" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2a01" size=" | + | |
caption="2a01, resolution 2.40Å" /> | caption="2a01, resolution 2.40Å" /> | ||
'''Crystal Structure of Lipid-free Human Apolipoprotein A-I'''<br /> | '''Crystal Structure of Lipid-free Human Apolipoprotein A-I'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Despite three decades of extensive studies on human apolipoprotein A-I | + | Despite three decades of extensive studies on human apolipoprotein A-I (apoA-I), the major protein component in high-density lipoproteins, the molecular basis for its antiatherogenic function is elusive, in part because of lack of a structure of the full-length protein. We describe here the crystal structure of lipid-free apoA-I at 2.4 A. The structure shows that apoA-I is comprised of an N-terminal four-helix bundle and two C-terminal helices. The N-terminal domain plays a prominent role in maintaining its lipid-free conformation, indicating that mutants with truncations in this region form inadequate models for explaining functional properties of apoA-I. A model for transformation of the lipid-free conformation to the high-density lipoprotein-bound form follows from an analysis of solvent-accessible hydrophobic patches on the surface of the structure and their proximity to the hydrophobic core of the four-helix bundle. The crystal structure of human apoA-I displays a hitherto-unobserved array of positively and negatively charged areas on the surface. Positioning of the charged surface patches relative to hydrophobic regions near the C terminus of the protein offers insights into its interaction with cell-surface components of the reverse cholesterol transport pathway and antiatherogenic properties of this protein. This structure provides a much-needed structural template for exploration of molecular mechanisms by which human apoA-I ameliorates atherosclerosis and inflammatory diseases. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2A01 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 AC9 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2A01 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=AC9:'>AC9</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A01 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Ajees, A | + | [[Category: Ajees, A A.]] |
| - | [[Category: Anantharamaiah, G | + | [[Category: Anantharamaiah, G M.]] |
| - | [[Category: Hussain, M | + | [[Category: Hussain, M M.]] |
| - | [[Category: Mishra, V | + | [[Category: Mishra, V K.]] |
| - | [[Category: Murthy, K | + | [[Category: Murthy, K H.M.]] |
[[Category: AC9]] | [[Category: AC9]] | ||
[[Category: four-helix bundle]] | [[Category: four-helix bundle]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:22:18 2008'' |
Revision as of 14:22, 21 February 2008
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Crystal Structure of Lipid-free Human Apolipoprotein A-I
Contents |
Overview
Despite three decades of extensive studies on human apolipoprotein A-I (apoA-I), the major protein component in high-density lipoproteins, the molecular basis for its antiatherogenic function is elusive, in part because of lack of a structure of the full-length protein. We describe here the crystal structure of lipid-free apoA-I at 2.4 A. The structure shows that apoA-I is comprised of an N-terminal four-helix bundle and two C-terminal helices. The N-terminal domain plays a prominent role in maintaining its lipid-free conformation, indicating that mutants with truncations in this region form inadequate models for explaining functional properties of apoA-I. A model for transformation of the lipid-free conformation to the high-density lipoprotein-bound form follows from an analysis of solvent-accessible hydrophobic patches on the surface of the structure and their proximity to the hydrophobic core of the four-helix bundle. The crystal structure of human apoA-I displays a hitherto-unobserved array of positively and negatively charged areas on the surface. Positioning of the charged surface patches relative to hydrophobic regions near the C terminus of the protein offers insights into its interaction with cell-surface components of the reverse cholesterol transport pathway and antiatherogenic properties of this protein. This structure provides a much-needed structural template for exploration of molecular mechanisms by which human apoA-I ameliorates atherosclerosis and inflammatory diseases.
Disease
Known diseases associated with this structure: Amyloidosis, 3 or more types OMIM:[107680], ApoA-I and apoC-III deficiency, combined OMIM:[107680], Corneal clouding, autosomal recessive OMIM:[107680], Hypertriglyceridemia, one form OMIM:[107680], Hypoalphalipoproteinemia OMIM:[107680]
About this Structure
2A01 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of human apolipoprotein A-I: insights into its protective effect against cardiovascular diseases., Ajees AA, Anantharamaiah GM, Mishra VK, Hussain MM, Murthy HM, Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2126-31. Epub 2006 Feb 1. PMID:16452169
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