Insight into the allosteric mechanism of Scapharca dimeric hemoglobin.
Insight into the allosteric mechanism of Scapharca dimeric hemoglobin.
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DOI：
10.1021/bi500591s
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发表时间：
2014-11-25
期刊：
影响因子：
2.9
通讯作者：
Massi, Francesca
中科院分区：
文献类型：
--
作者：
Laine, Jennifer M.;Amat, Miguel;Morgan, Brittany R.;Royer, William E., Jr.;Massi, Francesca
变构调节是许多蛋白质的基本功能，其控制各种不同的过程，如催化、信号转导和基因调节。结构重排历来被认为是蛋白质不同部分之间的主要通讯手段。然而，最近的研究强调了蛋白质柔性变化作为介导蛋白质变构通信的有效方式的重要性。Scapharca二聚血红蛋白（HbI）是最简单的可能的变构系统，具有两个相同亚基之间的合作配体结合。氧与HbI结合的热力学平衡研究表明，协同效应是一种熵驱动的效应。在配体结合时观察到的系统熵的变化可能是由系统的蛋白质、配体或水的变化引起的。本研究的目的是确定蛋白质骨架的熵变化对HbI协同结合的贡献。分子动力学模拟和核磁共振弛豫技术揭示了HbI的快速内部运动以两种方式促进了与一氧化碳的协同结合：（1）通过有利地促进系统的自由能和（2）通过参与HbI亚基界面的协同机制。用同样的方法研究了HbI弱合作突变体F97Y的内部动力学。F97 Y HbI在配体结合后观察到的骨架NH动力学的变化不如野生型大，这与该突变体观察到的协同性降低一致。本研究结果表明，界面柔性和骨架构象熵的HbI参与的一氧化碳结合的合作机制，是重要的。
Allosteric regulation is an essential function of many proteins that control a variety of different processes such as catalysis, signal transduction, and gene regulation. Structural rearrangements have historically been considered the main means of communication between different parts of a protein. Recent studies have highlighted the importance, however, of changes in protein flexibility as an effective way to mediate allosteric communication across a protein. Scapharca dimeric hemoglobin (HbI) is the simplest possible allosteric system, with cooperative ligand binding between two identical subunits. Thermodynamic equilibrium studies of the binding of oxygen to HbI have shown that cooperativity is an entropically driven effect. The change in entropy of the system observed upon ligand binding may arise from changes in the protein, the ligand, or the water of the system. The goal of this study is to determine the contribution of the change in entropy of the protein backbone to HbI cooperative binding. Molecular dynamics simulations and nuclear magnetic resonance relaxation techniques have revealed that the fast internal motions of HbI contribute to the cooperative binding to carbon monoxide in two ways: (1) by contributing favorably to the free energy of the system and (2) by participating in the cooperative mechanism at the HbI subunit interface. The internal dynamics of the weakly cooperative HbI mutant, F97Y, were also investigated with the same methods. The changes in backbone NH dynamics observed for F97Y HbI upon ligand binding are not as large as for the wild type, in agreement with the reduced cooperativity observed for this mutant. The results of this study indicate that interface flexibility and backbone conformational entropy of HbI participate in and are important for the cooperative mechanism of carbon monoxide binding.
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影响因子：
3.9
作者：
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通讯作者：
Kantrowitz, Evan R.
影响因子：
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作者：
LIPARI, G;SZABO, A
通讯作者：
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DOI：
10.1073/pnas.0509411103
发表时间：
2006-05-16
影响因子：
11.1
作者：
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通讯作者：
Royer, William E., Jr.
DOI：
10.1111/j.1749-6632.2011.06319.x
发表时间：
2012-01-01
期刊：
BLAVATNIK AWARDS FOR YOUNG SCIENTISTS 2011
影响因子：
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作者：
Kalodimos, Charalampos G.
通讯作者：
Kalodimos, Charalampos G.
影响因子：
2.9
作者：
FARROW, NA;MUHANDIRAM, R;KAY, LE
通讯作者：
KAY, LE