FORCING THERMODYNAMICALLY UNFOLDED PROTEINS TO FOLD

Citation
I. Baskakov et Dw. Bolen, FORCING THERMODYNAMICALLY UNFOLDED PROTEINS TO FOLD, The Journal of biological chemistry, 273(9), 1998, pp. 4831-4834
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
273
Issue
9
Year of publication
1998
Pages
4831 - 4834
Database
ISI
SICI code
0021-9258(1998)273:9<4831:FTUPTF>2.0.ZU;2-R
Abstract
A growing number of biologically important proteins have been identifi ed as fully unfolded or partially disordered, Thus, an intriguing ques tion is whether such proteins can be forced to fold by adding solutes found in the cells of some organisms, Nature has not ignored the power ful effect that the solution can have on protein stability and has dev eloped the strategy of using specific solutes (called organic osmolyte s) to maintain the structure and function cellular proteins in organis ms exposed to denaturing environmental stresses (Yancey, P. H., Clark, M. E., Hand, S. C., Bowlus, R. D., and Somero, G. N. (1982) Science 2 17, 1214-1222), Here, we illustrate the extraordinary capability of on e such osmolyte, trimethylamine N-oxide (TMAO), to force two thermodyn amically unfolded proteins to fold to nativelike species having signif icant functional activity, In one of these examples, TMAO is shown to increase the population of native state relative to the denatured ense mble by nearly five orders of magnitude, The ability of TMAO to force thermodynamically unstable proteins to fold presents an opportunity fo r structure determination and functional studies of an important emerg ing class of proteins that have little or no structure without the pre sence of TMAO.