Toward an atomistic description of the urea-denatured state of proteins

被引：56

作者：

Candotti, Michela ^{[1
,2
]}

Esteban-Martin, Santiago ^{[1
,2
]}

Salvatella, Xavier ^{[1
,2
,3
]}

Orozco, Modesto ^{[1
,2
,4
]}

机构：

[1] Inst Res Biomed Barcelona, Mol Modelling & Bioinformat Unit, Barcelona 08028, Spain

[2] Barcelona Supercomp Ctr, Computat Biol Program, Barcelona 08034, Spain

[3] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain

[4] Univ Barcelona, Fac Biol, Dept Bioquim, E-08028 Barcelona, Spain

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 15期

基金：

欧洲研究理事会;

关键词：

denaturing mechanism; protein unfolding; random coil; ensemble simulation; MOLECULAR-DYNAMICS SIMULATIONS; HYDROGEN-BONDS; DIPOLAR COUPLINGS; WATER-STRUCTURE; BETA-HAIRPIN; GUANIDINIUM; SOLVATION; NMR; SCATTERING; ENSEMBLE;

D O I：

10.1073/pnas.1216589110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We present here the characterization of the structural, dynamics, and energetics of properties of the urea-denatured state of ubiquitin, a small prototypical soluble protein. By combining state-of-the-art molecular dynamics simulations with NMR and small-angle X-ray scattering data, we were able to: (i) define the unfolded state ensemble, (ii) understand the energetics stabilizing unfolded structures in urea, (iii) describe the dedifferential nature of the interactions of the fully unfolded proteins with urea and water;and (iv) characterize the early stages of protein refolding when chemically denatured proteins are transferred to native conditions. The results presented herein are unique in providing a complete picture of the chemically unfolded state of proteins and contribute to deciphering the mechanisms that stabilize the native state of proteins, as well as those that maintain them unfolded in the presence of urea.

引用

页码：5933 / 5938

页数：6

共 49 条

[1] Physical interpretation of residual dipolar couplings in neutral aligned media [J].