...
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Molecular crowding enhances native state stability and refolding rates of globular proteins
【24h】

Molecular crowding enhances native state stability and refolding rates of globular proteins

机译:分子拥挤增强了球状蛋白的天然状态稳定性和复性速率

获取原文
获取原文并翻译 | 示例
           

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-β-sheet WW domain in the presence of large spherical particles whose interaction with the polypeptide chain is purely repulsive. At all volume fractions, φ_c, of the crowding agents the stability of the native state is enhanced. Remarkably, the refolding rates, which are larger than the value at φ_c = 0, increase nonmonotonically as φ_c increases, reaching a maximum at φ_c = φ_~*c At high values of φ_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 φ_c can be quantitatively mapped onto confinement in a volume-fraction-dependent spherical pore with radius R_s ≈ (4π/3φ_c)~(1/3) R_c (R_c) is the radius of the crowding particles) as long as φ_c ≤φ~*c. We show that the extent of native state stabilization at finite φ_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 φ_c = 0.
机译:细胞中大分子的存在在几何上限制了多肽链的可用空间。为了研究大分子拥挤对折叠热力学和动力学的影响,我们在存在大的球形颗粒(其与多肽链的相互作用纯粹是排斥的)的情况下,使用了全β-折叠WW域的非晶格模型。在所有体积分数的拥挤剂中,原始状态的稳定性得到增强。值得注意的是,重折叠率大于φ_c= 0时的值,随φ_c的增加而非单调增加,在φ_c=φ_〜* c时达到最大值。在φ_c的值较高时,耗尽诱导的分子内吸引力会产生结构紧凑且结构相当大的结构结构处于变性状态。 φ_c处的原始状态稳定性和折叠动力学的变化可以定量地映射到与体积分数相关的球形孔的限制中,半径为R_s≈(4π/3φ_c)〜(1/3)R_c(R_c)是拥挤半径粒子),只要φ_c≤φ〜* c。我们表明,在有限的φ_c处,本征态的稳定程度与球形孔中的稳定程度相当。在这两种情况下,速率提高是由于相对于φ_c= 0变性态的不稳定。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号