The H2A-H2B dimeric kinetic intermediate is stabilized by widespread hydrophobic burial with few fully native interactions.
The H2A-H2B dimeric kinetic intermediate is stabilized by widespread hydrophobic burial with few fully native interactions.
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H2A-H2B 二聚动力学中间体通过广泛的疏水埋藏而稳定，几乎没有完全天然的相互作用。
DOI：
10.1016/j.jmb.2011.11.032
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发表时间：
2012
影响因子：
5.6
通讯作者：
Gloss,LisaM
中科院分区：
文献类型：
--
作者：
Guyett,PaulJ;Gloss,LisaM
H2 A-H2 B组蛋白异二聚体通过单体和二聚体动力学中间体折叠。在0.5ms内，H2 A和H2 B多肽在几乎扩散限制的反应中缔合以形成二聚体系综，表示为I2和I2 ε，后者是以较高含量的非天然结构（NNS）为特征的亚群。I2合奏折叠到本地异源二聚体，N2，通过一个可观察到的，一阶动力学阶段。为了确定在I2合奏的结构区域，我们的特点是26丙氨酸突变体的埋疏水残基，跨越三个螺旋的典型组蛋白折叠的H2 A和H2 B和H2 B的C-末端螺旋。除了一个目标残基的I2，过渡态和N2的稳定性作出了显着贡献，但是，只有在二聚体界面的疏水性核心的残基扰动I2的双稳态人口。I2的不稳定与较慢的折叠速率相关，这意味着NNS不是一个动力学陷阱，而是加速折叠。Φ值的模式表明，在外围螺旋中形成分子内相互作用的残基贡献了与I2和N2相似的稳定性，但在疏水核心中参与分子间相互作用的残基仅在I2中部分折叠。这些发现提出了一个二聚然后重排模型。整个组蛋白折叠的残基有助于I2的稳定性，但在快速二聚化反应后，二聚体界面的疏水核心几乎没有完全天然的相互作用。在过渡态导致N2，更多的本地样的相互作用的开发和非本地的相互作用被重新安排。
The H2A–H2B histone heterodimer folds via monomeric and dimeric kinetic intermediates. Within ∼5 ms, the H2A and H2B polypeptides associate in a nearly diffusion limited reaction to form a dimeric ensemble, denoted I2and I2⁎, the latter being a subpopulation characterized by a higher content of nonnative structure (NNS). The I2ensemble folds to the native heterodimer, N2, through an observable, first-order kinetic phase. To determine the regions of structure in the I2ensemble, we characterized 26 Ala mutants of buried hydrophobic residues, spanning the three helices of the canonical histone folds of H2A and H2B and the H2B C-terminal helix. All but one targeted residue contributed significantly to the stability of I2, the transition state and N2; however, only residues in the hydrophobic core of the dimer interface perturbed the I2⁎population. Destabilization of I2⁎correlated with slower folding rates, implying that NNS is not a kinetic trap but rather accelerates folding. The pattern of Φ values indicated that residues forming intramolecular interactions in the peripheral helices contributed similar stability to I2and N2, but residues involved in intermolecular interactions in the hydrophobic core are only partially folded in I2. These findings suggest a dimerize-then-rearrange model. Residues throughout the histone fold contribute to the stability of I2, but after the rapid dimerization reaction, the hydrophobic core of the dimer interface has few fully native interactions. In the transition state leading to N2, more native-like interactions are developed and nonnative interactions are rearranged.
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影响因子：
6.8
作者：
Oliveberg, M
通讯作者：
Oliveberg, M
DOI：
10.1073/pnas.97.13.7084
发表时间：
2000-06-20
影响因子：
11.1
作者：
Grantcharova, VP;Riddle, DS;Baker, D
通讯作者：
Baker, D
a / b 结蛋白的二聚化对于结构和功能至关重要
DOI：
--
发表时间：
--
期刊：
影响因子：
--
作者：
Anna L. Mallam;S. Jackson
通讯作者：
S. Jackson
H2A 和 H2B 组蛋白单体稳定性的突变分析。
影响因子：
5.6
作者：
Stump,MatthewR;Gloss,LisaM
通讯作者：
Gloss,LisaM
RNase H 分层折叠的确认：蛋白质工程研究
DOI：
10.1038/12277
发表时间：
1999
期刊：
Nature Structural Biology
影响因子：
--
作者：
Tanya M. Raschke;Joan Kho;S. Marqusee
通讯作者：
S. Marqusee