Institute of Structural and Molecular Biology, Birkbeck College, University of London, London, United Kingdom.
Biophys J. 2013 Jun 4;104(11):2512-20. doi: 10.1016/j.bpj.2013.03.063.
The micro-exon genes (MEG) of Schistosoma mansoni, a parasite responsible for the second most widely spread tropical disease, code for small secreted proteins with sequences unique to the Schistosoma genera. Bioinformatics analyses suggest the soluble domain of the MEG-14 protein will be largely disordered, and using synchrotron radiation circular dichroism spectroscopy, its secondary structure was shown to be essentially completely unfolded in aqueous solution. It does, however, show a strong propensity to fold into more ordered structures under a wide range of conditions. Partial folding was produced by increasing temperature (in a reversible process), contrary to the behavior of most soluble proteins. Furthermore, significant folding was observed in the presence of negatively charged lipids and detergents, but not in zwitterionic or neutral lipids or detergents. Absorption onto a surface followed by dehydration stimulated it to fold into a helical structure, as it did when the aqueous solution was replaced by nonaqueous solvents. Hydration of the dehydrated folded protein was accompanied by complete unfolding. These results support the identification of MEG-14 as a classic intrinsically disordered protein, and open the possibility of its interaction/folding with different partners and factors being related to multifunctional roles and states within the host.
曼氏血吸虫的微外显子基因（MEG）是一种导致第二大流行热带病的寄生虫，其编码的小分泌蛋白具有曼氏血吸虫属特有的序列。生物信息学分析表明，MEG-14 蛋白的可溶性结构域将在很大程度上呈现无规则构象，而利用同步辐射圆二色性光谱，其二级结构在水溶液中基本上完全展开。然而，它确实表现出在广泛的条件下折叠成更有序结构的强烈倾向。通过升高温度（在一个可逆的过程中）产生部分折叠，这与大多数可溶性蛋白的行为相反。此外，在存在带负电荷的脂质和去污剂的情况下观察到显著的折叠，而在带中性或正电荷的脂质或去污剂中则没有。在吸收到表面后进行脱水刺激它折叠成螺旋结构，就像在将水溶液替换为非水溶液时一样。脱水折叠蛋白的水合伴随着完全展开。这些结果支持将 MEG-14 鉴定为经典的固有无序蛋白，并为其与不同的伙伴和因子的相互作用/折叠的可能性开辟了道路，这与宿主中的多功能作用和状态有关。
