Pressure-jump NMR study of dissociation and association of amyloid protofibrils
Pressure-jump NMR study of dissociation and association of amyloid protofibrils
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DOI：
10.1016/j.jmb.2005.04.010
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发表时间：
2005-06-24
影响因子：
5.6
通讯作者：
Akasaka, K
中科院分区：
文献类型：
--
作者：
Kamatari, YO;Yokoyama, S;Akasaka, K
淀粉样蛋白原纤维的解离和再结合过程中发起的压力跳已监测与实时H-1 NMR光谱使用固有变性的二硫键缺陷的母鸡溶菌酶的变体。在压力跳升至2kbar时，几个月内生长的成熟原纤维在几天内完全解离成单体。在压力跳降至30巴时，解离的单体立即开始重新缔合。缔合和解离循环可以通过交变压力可重复地重复，建立了一个概念，即原纤维的形成只是一个缓慢的动力学过程，达到热力学平衡。压力在控制原纤维形成中的突出的简单性和有效性为研究淀粉样蛋白原纤维形成反应的机制开辟了新的途径。压力诱导的解离速率与缔合反应的进展中所注意到的变化表明多个机制的伸长的原纤维。二硫键缺陷的鸡溶菌酶提供了一个特别简单的模型系统的热力学和动力学研究的原纤维形成，以及筛选药物的淀粉样变性。(c)2005爱思唯尔有限公司保留所有权利。
The dissociation and reassociation processes of amyloid protofibrils initiated by pressure-jump have been monitored with real-time H-1 NMR spectroscopy using an intrinsically denatured disulfide-deficient variant of hen lysozyme. Upon pressure-jump up to 2 kbar, the matured protofibrils grown over several months become fully dissociated into monomers within a few days. Upon pressure-jump down to 30 bar, the dissociated monomers immediately start reassociating. The association and dissociation cycle can be repeated reproducibly by alternating pressure, establishing a notion that the protofibril formation is simply a slow kinetic process toward thermodynamic equilibrium. The outstanding simplicity and effectiveness of pressure in controlling the protofibril formation opens a new route for investigating mechanisms of amyloid fibril-forming reactions. The noted variation in the pressure-induced dissociation rate with the progress of the association reaction suggests multiple mechanisms for the elongation of the protofibril. The disulfide-deficient hen lysozyme offers a particularly simple model system for thermodynamic and kinetic studies of protofibril formation as well as for screening drugs for amyloidosis. (c) 2005 Elsevier Ltd. All rights reserved.