Proteins with H-bond packing defects are highly interactive with lipid bilayers:: Implications for amyloidogenesis
Proteins with H-bond packing defects are highly interactive with lipid bilayers:: Implications for amyloidogenesis
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DOI：
10.1073/pnas.0335642100
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发表时间：
2003-03-04
影响因子：
11.1
通讯作者：
Berry, RS
中科院分区：
文献类型：
--
作者：
Fernández, A;Berry, RS
我们注意到，疾病相关的淀粉样蛋白，特别是细胞朊病毒蛋白具有最高比例的不完全去溶剂化的骨架H键可溶性蛋白质。这种键容易受到水的侵蚀，因此代表结构上的弱点。我们已经测量了蛋白质吸附到磷脂双分子层上，发现蛋白质的天然结构中的骨架H键的下包裹程度与其在双分子层上的沉积程度之间存在很强的相关性：H键包裹越少，蛋白质-双分子层结合的倾向就越高。这些观察结果支持这样的命题，即具有淀粉样蛋白生成倾向的可溶性蛋白和膜蛋白共享一个普遍的构建基序：下包裹的H键。然而在膜蛋白中，该基序并不表示结构脆弱性，在可溶性蛋白中，它负责它们的反应性。
We noticed that disease-related amyloidogenic proteins and especially cellular prion proteins have the highest proportion of incompletely desolvated backbone H bonds among soluble proteins. Such bonds are vulnerable to water attack and thus represent structural weaknesses. We have measured the adsorption of proteins onto phospholipid bilayers and found a strong correlation between the extent of underwrapping of backbone H bonds in the native structure of a protein and its extent of deposition on the bilayer: the less the H bond wrapping, the higher the propensity for protein-bilayer binding. These observations support the proposition that soluble proteins with amyloidogenic propensity and membrane proteins share a pervasive building motif: the under-wrapped H bonds. Whereas in membrane proteins, this motif does not signal a structural vulnerability, in soluble proteins, it is responsible for their reactivity.