1ya9

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{{STRUCTURE_1ya9| PDB=1ya9 | SCENE= }}
{{STRUCTURE_1ya9| PDB=1ya9 | SCENE= }}
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'''Crystal Structure of the 22kDa N-Terminal Fragment of Mouse Apolipoprotein E'''
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===Crystal Structure of the 22kDa N-Terminal Fragment of Mouse Apolipoprotein E===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_15890642}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15890642 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15890642}}
==About this Structure==
==About this Structure==
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[[Category: Apolipoprotein e]]
[[Category: Apolipoprotein e]]
[[Category: Ldl receptor binding]]
[[Category: Ldl receptor binding]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:04:02 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 18:39:31 2008''

Revision as of 15:39, 28 July 2008

Image:1ya9.gif

Template:STRUCTURE 1ya9

Crystal Structure of the 22kDa N-Terminal Fragment of Mouse Apolipoprotein E

Template:ABSTRACT PUBMED 15890642

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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