线圈的长度依赖 <-->在膜环境中的β-sheet过渡
Matthias Meier1, Joachim Seelig
1Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
Journal of the American Chemical Society
|January 1, 2008
概括
链的长度极大地影响了β片的形成,这是一个关键的蛋白质聚合物结构. 较长的 (n > 12) 在膜结合时容易形成β片,由驱动.
科学领域:
- 生物物理学的生物物理.
- 蛋白质折叠 蛋白质的折叠
- 膜生物物理学 膜生物物理学
背景情况:
- β片是蛋白质聚合物的主要结构元素.
- 在膜结合时折叠成β片的设计可以作为研究随机线圈到β结构过渡热力学模型.
研究的目的:
- 为了研究链长度对随机线圈到β-sheet过渡的影响.
- 为了阐明在膜相互作用过程中在设计中β片形成的热力学特征 ((KIGAKI) n).
主要方法:
- 循环二重化 (CD) 光谱法用于测量在脂质膜存在或不存在的情况下的β片含量.
- 异热定位热度计 (ITC) 确定了在用小单脂囊泡进行定位时的热力学结合参数.
- 合成了D-氨基酸替代物的类似物,以分离折叠反应的贡献.
主要成果:
- 贝塔叶形成表现出对链长度的合作依赖性,对于n>10-12的,观察到显著增加.
- 膜结合是一种由驱动的过程,以内热结合为特征.
- 对于n >= 12的,折叠反应在热力学上是有利的 (DeltaG°β ≈ -0.15 kcal/mol每残留物),由外热折叠驱动 (ΔH°β ≈ -0.2到 -0.6 kcal/mol每残留物),并通过不利的来抵消.
结论:
- 链长度是beta片形成和膜结合的关键决定因素.
- 在膜相互作用时,较长的 (n > = 12) 折叠成β片是热力学上有利的.
- 微妙的环境变化 (pH,温度) 可以显著影响聚合和粉样纤维的形成,由于这些过渡的敏感性.
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