Hydrophobic Collapse of Trigger Factor Monomer in Solution

被引:10
作者
Singhal, Kushagra [1 ]
Vreede, Jocelyne [1 ]
Mashaghi, Alireza [2 ]
Tans, Sander J. [2 ]
Bolhuis, Peter G. [1 ]
机构
[1] Univ Amsterdam, vant Hoff Inst Mol Sci, Amsterdam, Netherlands
[2] FOM Inst AMOLF, Dept Syst Biophys, Amsterdam, Netherlands
关键词
C-TERMINAL DOMAIN; ESCHERICHIA-COLI; NASCENT CHAIN; FUNCTIONAL DISSECTION; MOLECULAR CHAPERONES; FORCE-FIELD; PROTEINS; RECOGNITION; RIBOSOME; BINDING;
D O I
10.1371/journal.pone.0059683
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
Trigger factor (TF) is a chaperone, found in bacterial cells and chloroplasts, that interacts with nascent polypeptide chains to suppress aggregation. While its crystal structure has been resolved, the solution structure and dynamics are largely unknown. We performed multiple molecular dynamics simulations on Trigger factor in solution, and show that its tertiary domains display collective motions hinged about inter-domain linkers with minimal or no loss in secondary structure. Moreover, we find that isolated TF typically adopts a collapsed state, with the formation of domain pairs. This collapse of TF in solution is induced by hydrophobic interactions and stabilised by hydrophilic contacts. To determine the nature of the domain interactions, we analysed the hydrophobicity of the domain surfaces by using the hydrophobic probe method of Acharya et al. [1,2], as the standard hydrophobicity scales predictions are limited due to the complex environment. We find that the formation of domain pairs changes the hydrophobic map of TF, making the N-terminal and arm2 domain pair more hydrophilic and the head and arm1 domain pair more hydrophobic. These insights into the dynamics and interactions of the TF domains are important to eventually understand chaperone-substrate interactions and chaperone function.
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页数:11
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