淀粉样蛋白纤维化的停-去动力学
Stop-and-go kinetics in amyloid fibrillation
摘要：
许多人类疾病与蛋白质聚集和纤维化有关。我们目前的实验在体外胰高血糖素纤维化使用全内反射荧光显微镜，提供实时测量单纤维生长。我们发现淀粉样纤维以间歇性的方式生长，生长期之后是长时间的停顿。所观察到的指数分布的停止和生长时间支持马尔可夫模型，在该模型中，原纤维在两个状态之间以特定的速率移动。值得注意的是，在所有实验中，处于增长（停止）状态的概率非常接近1/4（3/4），即使速率变化很大。这一发现表明存在4个独立的构象的原纤维尖端，我们讨论了这种可能性，在现有的结构知识。
英文摘要：
Many human diseases are associated with protein aggregation and fibrillation. We present experiments on in vitro glucagon fibrillation using total internal reflection fluorescence microscopy, providing real-time measurements of single-fibril growth. We find that amyloid fibrils grow in an intermittent fashion, with periods of growth followed by long pauses. The observed exponential distributions of stop and growth times support a Markovian model, in which fibrils shift between the two states with specific rates. Remarkably, the probability of being in the growing (stopping) state is very close to 1/4 (3/4) in all experiments, even if the rates vary considerably. This finding suggests the presence of 4 independent conformations of the fibril tip; we discuss this possibility in terms of the existing structural knowledge.
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