Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology RAS, Tikhoretsky Ave. 4, St. Petersburg 194064, Russia.
Prog Biophys Mol Biol. 2010 Jun-Jul;102(2-3):73-84. doi: 10.1016/j.pbiomolbio.2010.01.003. Epub 2010 Jan 25.
The native state of a protein is usually associated with a compact globular conformation possessing a rigid and highly ordered structure. At the turn of the last century certain studies arose which concluded that many proteins cannot, in principle, form a rigid globular structure in an aqueous environment, but they are still able to fulfill their specific functions--i.e., they are native. The existence of the disordered regions allows these proteins to interact with their numerous binding partners. Such interactions are often accompanied by the formation of complexes that possess a more ordered structure than the original components. The functional diversity of these proteins, combined with the variability of signals related to the various intra- and intercellular processes handled by these proteins and their capability to produce multi-variant and multi-directional responses allow them to form a unique regulatory net in a cell. The abundance of disordered proteins inside the cell is precisely controlled at the synthesis and clearance levels as well as via interaction with specific binding partners and post-translational modifications. Another recently recognized biologically active state of proteins is the functional amyloid. The formation of such functional amyloids is tightly controlled and therefore differs from the uncontrolled formation of pathogenic amyloids which are associated with the pathogenesis of several conformational diseases, the development of which is likely to be determined by the failures of the cellular regulatory systems rather than by the formation of the proteinaceous deposits and/or by the protofibril toxicity.
蛋白质的天然状态通常与其紧凑的球状构象相关联，这种构象具有刚性和高度有序的结构。在上个世纪之交，出现了某些研究结论，即许多蛋白质在水相环境中原则上不能形成刚性的球状结构，但它们仍然能够发挥其特定的功能——即它们是天然的。无定形区域的存在允许这些蛋白质与其众多的结合伙伴相互作用。这种相互作用通常伴随着复合物的形成，复合物具有比原始成分更有序的结构。这些蛋白质的功能多样性，加上与这些蛋白质处理的各种细胞内和细胞间过程相关的信号的可变性，以及它们产生多变量和多方向反应的能力，使它们能够在细胞中形成独特的调控网络。无序蛋白质在细胞内的丰度在合成和清除水平以及通过与特定结合伙伴的相互作用和翻译后修饰得到精确控制。蛋白质的另一种最近被识别的生物活性状态是功能性淀粉样蛋白。这种功能性淀粉样蛋白的形成受到严格控制，因此与无控制形成的致病性淀粉样蛋白不同，后者与几种构象疾病的发病机制有关，这些疾病的发展可能是由细胞调控系统的故障而不是由蛋白质沉积物的形成和/或原纤维毒性决定的。
