Entropic mechanism of large fluctuation in allosteric transition

被引：46

作者：

Itoh, Kazuhito ^{[1
]}

Sasai, Masaki ^{[1
,2
]}

机构：

[1] Nagoya Univ, Dept Appl Phys, Nagoya, Aichi 4648603, Japan

[2] Korea Inst Adv Study, Seoul 130722, South Korea

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 17期

基金：

新加坡国家研究基金会; 日本学术振兴会;

关键词：

free-energy landscape; population shift; statistical mechanical model; REGULATORY PROTEIN-C; CONFORMATIONAL DYNAMICS; SIGNALING PROTEIN; ENERGY LANDSCAPES; ADENYLATE KINASE; NMR-SPECTROSCOPY; FOLDING FUNNELS; RECEIVER DOMAIN; MODEL; PATHWAYS;

D O I：

10.1073/pnas.0912978107

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：

A statistical mechanical model of allosteric transitions in proteins is developed by extending the structure-based model of protein folding to cases of multiple native conformations. The partition function is calculated exactly within the model and the free-energy surface reflecting allostery is derived. This approach is applied to an example protein, the receiver domain of the bacterial enhancer-binding protein NtrC. The model predicts the large entropy associated with a combinatorial number of preexisting transition routes. This large entropy lowers the free-energy barrier of the allosteric transition, which explains the large structural fluctuation observed in the NMR data of NtrC. The global allosteric transformation of NtrC is explained by the shift of preexisting distribution of conformations upon phosphorylation, but the local structural adjustment around the phosphorylation site is explained by the complementary induced-fit mechanism. Structural disordering accompanied by fluctuating interactions specific to two allosteric conformations underlies a large number of routes of allosteric transition.

引用

页码：7775 / 7780

页数：6

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