Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
Langmuir. 2013 Jan 8;29(1):365-70. doi: 10.1021/la304374q. Epub 2012 Dec 26.
Formation of amyloid fibrils is often associated with intriguing far-from-equilibrium phenomena such as conformational memory effects or flow-driven self-assembly. Insulin is a model amyloidogenic polypeptide forming distinct structural variants of fibrils, which self-propagate through seeding. According to infrared absorption, fibrils from bovine insulin ([BI]) and Lys(B31)-Arg(B32) human insulin analogue ([KR]) cross-seed each other and imprint distinct structural features in daughter fibrils. In the absence of preformed [KR] amyloid seeds, bovine insulin agitated at 60 °C converts into chiral amyloid superstructures exhibiting negative extrinsic Cotton effect in bound thioflavin T. However, when agitated bovine insulin is simultaneously cross-seeded with [KR] amyloid, daughter fibrils reveal a positive extrinsic Cotton effect. Our study indicates that dramatic changes in global properties of amyloid superstructures may emerge from subtle conformational-level variations in single fibrils (e.g., alignment and twist of β-strands) that are encoded by memory effects.
淀粉样纤维的形成通常与有趣的远离平衡现象有关，如构象记忆效应或流动驱动的自组装。胰岛素是一种模型淀粉样多肽，可形成不同结构的纤维变体，通过接种自我传播。根据红外吸收，来自牛胰岛素（[BI]）和 Lys（B31）-Arg（B32）人胰岛素类似物（[KR]）的纤维彼此交叉，并在子纤维中留下独特的结构特征。在没有预形成的 [KR]淀粉样种子的情况下，在 60°C 下搅拌的牛胰岛素转化为手性淀粉样超结构，在结合的硫代黄素 T 中表现出负的外源性 Cotton 效应。然而，当搅拌的牛胰岛素同时与 [KR]淀粉样交叉接种时，子纤维显示出正的外源性 Cotton 效应。我们的研究表明，淀粉样超结构的整体性质的巨大变化可能源于单根纤维中细微的构象水平变化（例如，β-链的排列和扭曲），这些变化由记忆效应编码。
