1ya9
From Proteopedia
(New page: 200px<br /><applet load="1ya9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ya9, resolution 2.09Å" /> '''Crystal Structure of...) |
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| - | [[Image:1ya9.gif|left|200px]]<br /><applet load="1ya9" size=" | + | [[Image:1ya9.gif|left|200px]]<br /><applet load="1ya9" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ya9, resolution 2.09Å" /> | caption="1ya9, resolution 2.09Å" /> | ||
'''Crystal Structure of the 22kDa N-Terminal Fragment of Mouse Apolipoprotein E'''<br /> | '''Crystal Structure of the 22kDa N-Terminal Fragment of Mouse Apolipoprotein E'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Apolipoprotein (apo) E4 is a major risk factor for Alzheimer and | + | Apolipoprotein (apo) E4 is a major risk factor for Alzheimer and cardiovascular diseases. ApoE4 differs from the two other common isoforms (apoE2 and apoE3) by its lower resistance to denaturation and greater propensity to form partially folded intermediates. As a first step to determine the importance of stability differences in vivo, we reengineered a partially humanized variant of the amino-terminal domain of mouse apoE (T61R mouse apoE) to acquire a destabilized conformation like that of apoE4. For this process, we determined the crystal structure of wild-type mouse apoE, which, like apoE4, forms a four-helix bundle, and identified two structural differences in the turn between helices 2 and 3 and in the middle of helix 3 as potentially destabilizing sites. Introducing mutations G83T and N113G at these sites destabilized the mouse apoE conformation. The mutant mouse apoE more rapidly remodeled phospholipid than T61R mouse apoE, which supports the hypothesis that a destabilized conformation promotes apoE4 lipid binding. |
==About this Structure== | ==About this Structure== | ||
| - | 1YA9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http:// | + | 1YA9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YA9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Hatters, D | + | [[Category: Hatters, D M.]] |
[[Category: Newhouse, Y.]] | [[Category: Newhouse, Y.]] | ||
| - | [[Category: Peters-Libeu, C | + | [[Category: Peters-Libeu, C A.]] |
[[Category: Rutenber, E.]] | [[Category: Rutenber, E.]] | ||
| - | [[Category: Weisgraber, K | + | [[Category: Weisgraber, K H.]] |
[[Category: apolipoprotein e]] | [[Category: apolipoprotein e]] | ||
[[Category: ldl receptor binding]] | [[Category: ldl receptor binding]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:03:18 2008'' |
Revision as of 14:03, 21 February 2008
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Crystal Structure of the 22kDa N-Terminal Fragment of Mouse Apolipoprotein E
Overview
Apolipoprotein (apo) E4 is a major risk factor for Alzheimer and cardiovascular diseases. ApoE4 differs from the two other common isoforms (apoE2 and apoE3) by its lower resistance to denaturation and greater propensity to form partially folded intermediates. As a first step to determine the importance of stability differences in vivo, we reengineered a partially humanized variant of the amino-terminal domain of mouse apoE (T61R mouse apoE) to acquire a destabilized conformation like that of apoE4. For this process, we determined the crystal structure of wild-type mouse apoE, which, like apoE4, forms a four-helix bundle, and identified two structural differences in the turn between helices 2 and 3 and in the middle of helix 3 as potentially destabilizing sites. Introducing mutations G83T and N113G at these sites destabilized the mouse apoE conformation. The mutant mouse apoE more rapidly remodeled phospholipid than T61R mouse apoE, which supports the hypothesis that a destabilized conformation promotes apoE4 lipid binding.
About this Structure
1YA9 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Engineering conformational destabilization into mouse apolipoprotein E. A model for a unique property of human apolipoprotein E4., Hatters DM, Peters-Libeu CA, Weisgraber KH, J Biol Chem. 2005 Jul 15;280(28):26477-82. Epub 2005 May 11. PMID:15890642
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