Structural Heterogeneity of Human Histone H2A.1.
Structural Heterogeneity of Human Histone H2A.1.
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DOI：
10.1021/acs.jpcb.1c00335
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发表时间：
2021-05-20
期刊：
影响因子：
--
通讯作者：
Fernandez-Lima F
中科院分区：
文献类型：
--
作者：
Pham KN;Mamun Y;Fernandez-Lima F
组蛋白是高度碱性的染色质蛋白质，其将真核生物DNA紧密包装和排序成核小体。虽然核小体的原子结构已经确定，但无DNA组蛋白的三维结构仍然没有得到解决。在这里，我们结合联合收割机串联非线性和线性离子迁移谱（FAIMS-TIMS）耦合质谱与分子模拟并行研究的构象空间的DNA-自由组蛋白H2 A 1型（H2A.1）。实验结果表明，依赖的气相结构与起始溶液的条件，其特征在于电荷态分布，迁移率分布，碰撞诱导展开（CIU）的途径。测量的H2A.1气相结构显示出高度多样性的结构特征，从紧凑到部分折叠，然后高度伸长的构象。分子动力学模拟提供了候选结构的解决方案H2A.1天然构象与折叠的N-和C-末端的尾巴，以及气相候选结构与流动性的趋势。互补的CCS和偶极计算表明，在细长的气相结构的情况下，其中碱性和酸性残基大部分暴露（例如，z > 15+），足以在高电场下引起偶极排列的差异，与FAIMS-TIMS实验期间观察到的趋势非常一致。
Histones are highly basic chromatin proteins that tightly package and order eukaryotic DNA into nucleosomes. While the atomic structure of the nucleosomes has been determined, the three-dimensional structure of DNA-free histones remains unresolved. Here, we combine tandem non-linear and linear ion mobility spectrometry (FAIMS-TIMS) coupled to mass spectrometry in parallel with molecular modeling to study the conformational space of a DNA-free histone H2A type 1 (H2A.1). Experimental results showed the dependence of the gas-phase structures with the starting solution conditions, characterized by charge state distributions, mobility distributions, and collision-induced-unfolding (CIU) pathways. The measured H2A.1 gas-phase structures showed a high diversity of structural features ranging from compact to partially folded, and then highly elongated conformations. Molecular dynamic simulations provided candidate structures for the solution H2A.1 native conformation with folded N- and C-terminal tails, as well as gas-phase candidate structures associated with the mobility trends. Complementary CCS and dipole calculations showed that the charge distribution in the case of elongated gas-phase structures, where basic and acidic residues are mostly exposed (e.g., z > 15+), is sufficient to induce differences in the dipole alignment at high electric fields, in good agreement with the trends observed during the FAIMS-TIMS experiments.
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DOI：
10.1007/s13361-014-0941-9
发表时间：
2014-09
影响因子：
3.2
作者：
Isenberg, Samantha L.;Armistead, Paul M.;Glish, Gary L.
通讯作者：
Glish, Gary L.
影响因子：
7.4
作者：
Jeanne Dit Fouque K;Garabedian A;Leng F;Tse-Dinh YC;Ridgeway ME;Park MA;Fernandez-Lima F
通讯作者：
Fernandez-Lima F
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1021/acs.jpcb.0c04276
发表时间：
2020-07-23
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Jeanne Dit Fouque K;Fernandez-Lima F
通讯作者：
Fernandez-Lima F
影响因子：
3.3
作者：
Fouque, Kevin Jeanne Dit;Moreno, Javier;Fernandez-Lima, Francisco
通讯作者：
Fernandez-Lima, Francisco