Amyloidogenesis in its biological environment: challenging a fundamental issue in protein misfolding diseases
Amyloidogenesis in its biological environment: challenging a fundamental issue in protein misfolding diseases
复制标题
DOI：
10.1016/j.sbi.2008.10.001
复制
发表时间：
2008-12-01
影响因子：
6.8
通讯作者：
Chiti, Fabrizio
中科院分区：
文献类型：
--
作者：
Bellotti, Vittorio;Chiti, Fabrizio
蛋白质不能采用其天然和可溶性构象（蛋白质错误折叠）是越来越多的人类疾病的起源。蛋白质的错误折叠通常与其组装成细胞外原纤维聚集体（通常称为淀粉样原纤维）有关。尽管在体外对淀粉样蛋白的形成进行了许多努力，但越来越明显的是，聚集发生的生物环境自然地影响该过程的机制和速率，以及所得原纤维的结构和稳定性。这个问题并不是微不足道的，因为生物学的固有复杂性和设计能够解决体内现象的分子水平的适当实验的困难。我们将展示最近使用的成功方法，并将说明一些有助于阐明体内淀粉样蛋白形成的重要结构方面的结果。
The inability of a protein to adopt its native and soluble conformation (protein misfolding) is the origin of an increasing number of human diseases. The misfolding of a protein is often associated with its assembly into extracellular fibrillar aggregates, commonly termed amyloid fibrils. Despite the many efforts expended to characterise amyloid formation in vitro, it is increasingly evident that the biological environment in which aggregation occurs naturally influences the mechanism and rate of the process, as well as the structure and stability of the resulting fibrils. This problem is not trivial because of the inherent complexity of biology and difficulty to design proper experiments able to address the molecular level of the phenomenon in vivo. We will show successful approaches that have been used recently and will illustrate some of the results that have contributed to elucidate important structural aspects of amyloid formation in vivo.