Departamento Bioquímica de la Nutrición, Instituto Superior de Investigaciones Biológicas, Tucumán, Argentina.
Curr Protein Pept Sci. 2011 May;12(3):166-80. doi: 10.2174/138920311795860197.
Even though our knowledge of how proteins misfold and aggregate is deeper nowadays, the mechanisms driving this process are still poorly understood. Among the factors involved, membranes should be taken into account. Indeed, convincing evidence suggests that membranes may influence protein folding, misfolding and aggregation. In fact, membrane lipid composition of different cellular types may attenuate or intensify the environmental pressure over protein folding equilibrium. In the present review the aim is to make an up-to-date analysis of the membrane influence on protein aggregation from a biophysical point of view in order to provide useful tools for researchers from other fields. In particular, we discuss how membranes can alter protein environment, e.g. increasing local protein concentration, lowering pH and dielectric constant, allowing accessibility to the hydrophobic milieu and promoting surface crowding, all of which will lead to protein aggregation. In addition, we review the role that specific lipids may exert on protein aggregation and finally we analyse the possible implication of membrane-related oxidative stress on amyloidogenesis.
尽管我们现在对蛋白质错误折叠和聚集的机制有了更深入的了解，但驱动这一过程的机制仍知之甚少。在涉及的因素中，应该考虑到膜。事实上，令人信服的证据表明，膜可能会影响蛋白质的折叠、错误折叠和聚集。事实上，不同细胞类型的膜脂组成可能会减轻或加剧蛋白质折叠平衡的环境压力。在本综述中，我们的目的是从生物物理的角度对膜对蛋白质聚集的影响进行最新分析，为来自其他领域的研究人员提供有用的工具。特别是，我们讨论了膜如何改变蛋白质环境，例如增加局部蛋白质浓度、降低 pH 值和介电常数、允许接近疏水环境并促进表面拥挤，所有这些都会导致蛋白质聚集。此外，我们还回顾了特定脂质可能对蛋白质聚集产生的作用，最后我们分析了与膜相关的氧化应激对淀粉样变性的可能影响。
