期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：13
页码：4753-4758
DOI：10.1073/pnas.0409630102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The presence of macromolecules in cells geometrically restricts the available space for poplypeptide chains. To study the effects of macromolecular crowding on folding thermodynamics and kinetics, we used an off-lattice model of the all-{beta}-sheet WW domain in the presence of large spherical particles whose interaction with the polypeptide chain is purely repulsive. At all volume fractions, {varphi}c, of the crowding agents the stability of the native state is enhanced. Remarkably, the refolding rates, which are larger than the value at {varphi}c = 0, increase nonmonotonically as {varphi}c increases, reaching a maximum at [IMG]f1.gif" BORDER="0">. At high values of {varphi}c, the depletion-induced intramolecular attraction produces compact structures with considerable structure in the denatured state. Changes in native state stability and folding kinetics at {varphi}c can be quantitatively mapped onto confinement in a volume-fraction-dependent spherical pore with radius Rs {approx} (4{pi}/3{varphi}c)1/3 Rc (Rc is the radius of the crowding particles) as long as [IMG]f2.gif" BORDER="0">. We show that the extent of native state stabilization at finite {varphi}c is comparable with that in a spherical pore. In both situations, rate enhancement is due to destabilization of the denatured states with respect to {varphi}c = 0.
关键词：confinement effects ; protein folding ; depletion-interaction
