科研之友
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摘要
Attempts to understand the biophysical foundations and biochemical consequences of protein aggregation process are greatly aided by conditions which provide either robust and reliable reaction conditions or constitute mimics of the physiological conditions. While both anionic surfactants such as SDS and fluorinated alcohols such as TFE are often championed as membrane mimics in one way or another, it is probably fair to say that their greatest advantage is to facilitate protein aggregation under simple and well-defined solvent conditions which are compatible with a plethora of biophysical techniques. In contrast to the biological membrane, whose chemical complexity and physical heterogeneity gives rise to a multitude of possible interactions with proteins, SDS and TFE exert a surprisingly versatile effect on proteins by a combination of two opposing forces: a weakening of protein-protein hydrophobic interactions and a strengthening of inter- and intra-molecular hydrogen bonding. This invariably gives rise to a concentration range (typically 0.5-1 mM SDS and 20-30% TFE) which favours intermolecular beta-sheet formation. I discuss a number of examples of this behaviour, and present recent investigations based on a combination of calorimetric, spectroscopic and Small Angle X-ray scattering techniques. Together these provide a structural and stoichiometric picture of the different species involved in SDS-mediated protein aggregation, driven by the hydrophobic bonds formed when SDS clusters on different proteins form a contiguous micelle by protein association. Higher-order aggregates are formed by protein regions linking these shared micelles, providing a flexible bead-on-a-string that grows in a step-wise fashion and leads to worm-like fibrillar structures. Despite the unique features displayed in different aggregating systems, there are clear parallels between membrane-mediated aggregation and aggregation in SDS and TFE in terms of modulation between alpha-helical and beta-sheet structures depending on the ratio between protein and amphiphile.
- 出版日期2010-8
