Baskakov I, Bolen D W
Department of Human Biological Chemistry and Genetics, Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, Texas 77555-1052, USA.
J Biol Chem. 1998 Feb 27;273(9):4831-4. doi: 10.1074/jbc.273.9.4831.
A growing number of biologically important proteins have been identified as fully unfolded or partially disordered. Thus, an intriguing question is whether such proteins can be forced to fold by adding solutes found in the cells of some organisms. Nature has not ignored the powerful effect that the solution can have on protein stability and has developed the strategy of using specific solutes (called organic osmolytes) to maintain the structure and function cellular proteins in organisms exposed to denaturing environmental stresses (Yancey, P. H., Clark, M. E., Hand, S. C., Bowlus, R. D., and Somero, G. N. (1982) Science 217, 1214-1222). Here, we illustrate the extraordinary capability of one such osmolyte, trimethylamine N-oxide (TMAO), to force two thermodynamically unfolded proteins to fold to native-like species having significant functional activity. In one of these examples, TMAO is shown to increase the population of native state relative to the denatured ensemble by nearly five orders of magnitude. The ability of TMAO to force thermodynamically unstable proteins to fold presents an opportunity for structure determination and functional studies of an important emerging class of proteins that have little or no structure without the presence of TMAO.
越来越多具有生物学重要性的蛋白质已被鉴定为完全未折叠或部分无序。因此，一个有趣的问题是，通过添加某些生物体细胞中存在的溶质，是否可以迫使这类蛋白质折叠。大自然并未忽视溶液对蛋白质稳定性可能产生的强大影响，并已开发出利用特定溶质（称为有机渗透剂）的策略，以在暴露于变性环境压力的生物体中维持细胞蛋白质的结构和功能（扬西，P.H.，克拉克，M.E.，汉德，S.C.，鲍卢斯，R.D.，和索梅罗，G.N.（1982年）《科学》217，1214 - 1222）。在此，我们展示了一种这样的渗透剂——三甲胺N - 氧化物（TMAO）——迫使两种热力学上未折叠的蛋白质折叠成具有显著功能活性的类似天然状态物种的非凡能力。在其中一个例子中，相对于变性整体，TMAO使天然状态的群体增加了近五个数量级。TMAO迫使热力学不稳定蛋白质折叠的能力为一类重要的新兴蛋白质的结构测定和功能研究提供了机会，这类蛋白质在没有TMAO的情况下几乎没有或没有结构。
