Thermodynamic analysis of amyloid fibril structures reveals a common framework for stability in amyloid polymorphs.
Thermodynamic analysis of amyloid fibril structures reveals a common framework for stability in amyloid polymorphs.
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淀粉样蛋白原纤维结构的热力学分析揭示了淀粉样蛋白多晶型物稳定性的共同框架。
DOI：
10.1016/j.str.2022.05.002
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发表时间：
2022
期刊：
影响因子：
5.7
通讯作者：
F. Rousseau
中科院分区：
文献类型：
--
作者：
R. van der Kant;Nikolaos N. Louros;J. Schymkowitz;F. Rousseau
淀粉样蛋白结构数量的增加为研究决定淀粉样蛋白稳定性和多态性的一般原理提供了机会。我们发现淀粉样蛋白的稳定性由约30%的残基控制，这些残基位于有利于交叉β构象的片段上。这些与已知的聚集成核区相对应，并构成了一个稳定的跨β结构框架，该框架在多晶之间共享。这些片段在原丝内的结构受挫区域的替代包装导致构象不同，但能量相似的多晶体。淀粉样蛋白和球状结构中原子间距离分布的差异分析表明，非常规的残馀接触，如近距离的相同电荷，位于淀粉样蛋白的能量受挫段。这些观察结果表明，多态性是由高交叉β倾向的保守稳定区域组成的框架机制造成的。这些区域散布着结构不理想的区域，这些区域是构象可塑性和与稳定辅助因子（如（多）离子）相互作用的潜在位点。
The increasing number of amyloid structures offers an opportunity to investigate the general principles determining amyloid stability and polymorphism. We find that amyloid stability is dominated by ∼30% of residues localized in segments that favor the cross-β conformation. These correspond to known aggregation-nucleating regions and constitute a stabilizing cross-β structural framework that is shared among polymorphs. Alternative packing of these segments with structurally frustrated regions within the protofilament results in conformationally different, but energetically similar, polymorphs. Differential analysis of distributions of interatomic distances in amyloid and globular structures revealed that unconventional residue contacts, such as identical charges in close proximity, are located in energetically frustrated segments of amyloids. These observations suggest that polymorphism results from a framework mechanism consisting of conserved stabilizing regions of high cross-β propensity. These are interspersed by structurally suboptimal regions that are potential sites of conformational plasticity and interaction with stabilizing cofactors such as (poly)ions.
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影响因子：
5
作者：
Illes-Toth E;Rempel DL;Gross ML
通讯作者：
Gross ML
影响因子：
13.6
作者：
Antonschmidt L;Dervişoğlu R;Sant V;Tekwani Movellan K;Mey I;Riedel D;Steinem C;Becker S;Andreas LB;Griesinger C
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影响因子：
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作者：
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