1YA9

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

1YA9 の概要

• エントリーDOI: 10.2210/pdb1ya9/pdb
• 分子名称: Apolipoprotein E (2 entities in total)
• 機能のキーワード: apolipoprotein e, ldl receptor binding, lipid transport
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21052.61

構造登録者

Peters-Libeu, C.A.,Rutenber, E.,Newhouse, Y.,Hatters, D.M.,Weisgraber, K.H. (登録日: 2004-12-17, 公開日: 2005-06-07, 最終更新日: 2024-02-14)

主引用文献

Hatters, D.M.,Peters-Libeu, C.A.,Weisgraber, K.H.
Engineering conformational destabilization into mouse apolipoprotein E. A model for a unique property of human apolipoprotein E4
J.Biol.Chem., 280:26477-26482, 2005

PubMed Abstract: 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.

PubMed: 15890642
DOI: 10.1074/jbc.M503910200

実験手法

X-RAY DIFFRACTION (2.09 Å)