The N-terminal tails of the H2A-H2B histones affect dimer structure and stability.
The N-terminal tails of the H2A-H2B histones affect dimer structure and stability.
复制标题
H2A-H2B 组蛋白的 N 末端尾部影响二聚体结构和稳定性。
DOI：
10.1021/bi026283k
复制
发表时间：
2002
期刊：
影响因子：
2.9
通讯作者：
L. Gloss
中科院分区：
文献类型：
--
作者：
B. Placek;L. Gloss
核心核小体的组蛋白是高度碱性的，并在“握手模体”中形成异二聚体。组蛋白的N端延伸到握手基序的组蛋白折叠之外，是翻译后修饰的位置，包括赖氨酸乙酰化和丝氨酸磷酸化，这些修饰影响染色质的结构和活性，并改变尾巴的电荷状态。然而，目前尚不清楚这些修饰是否是募集其他细胞因子的信号，或者从N末端尾部移除净正电荷是否在染色质的整体结构中发挥作用。为了阐明N-末端对组蛋白结构和稳定性的影响，从H_2A和H_2B组蛋白中截断了高电荷的N-末端。研究了三种突变二聚体：Deltan-H_2A/Wt H_2B、Wt_2A/Deltan-H_2B和Deltan-H_2A/Deltan-H_2B。比较了三种截短型二聚体与野生型二聚体的圆二聚体光谱、对尿素变性的稳定性以及对盐的稳定性。这些数据支持关于H_2A和H_2B的N-末端的影响的四个结论：(1)去除H_2A和H_2B的N-末端可以增强突变的杂二聚体的螺旋结构。(2)相对于全长WT杂二聚体，Deltan-H_2A/WT H_2B二聚体是不稳定的，而WT H_2A/Deltan-H_2B和Deltan-H_2A/Deltan-H_2B二聚体略有稳定。(3)与WT二聚体相比，截短二聚体的m值降低，支持分离二聚体的N-末端采用折叠结构的假说。(4)N-末端的静电斥力降低了H_2A-H_2B二聚体的稳定性。
The histone proteins of the core nucleosome are highly basic and form heterodimers in a "handshake motif." The N-terminal tails of the histones extend beyond the canonical histone fold of the hand-shake motif and are the sites of posttranslational modifications, including lysine acetylations and serine phosphorylations, which influence chromatin structure and activity as well as alter the charge state of the tails. However, it is not well understood if these modifications are signals for recruitment of other cellular factors or if the removal of net positive charge from the N-terminal tail plays a role in the overall structure of chromatin. To elucidate the effects of the N-terminal tails on the structure and stability of histones, the highly charged N-terminal tails were truncated from the H2A and H2B histones. Three mutant dimers were studied: DeltaN-H2A/WT H2B; WT H2A/DeltaN-H2B, and DeltaN-H2A/DeltaN-H2B. The CD spectra, stabilities to urea-denaturation, and the salt-dependent stabilization of the three truncated dimers were compared with those of the wild-type dimer. The data support four conclusions regarding the effects of the N-terminal tails of H2A and H2B: (1) Removal of the N-terminal tails of H2A and H2B enhance the helical structure of the mutant heterodimers. (2) Relative to the full-length WT heterodimer, the DeltaN-H2A/WT H2B dimer is destabilized, while the WT H2A/DeltaN-H2B and DeltaN-H2A/DeltaN-H2B dimers are slightly stabilized. (3) The truncated dimers exhibit decreased m values, relative to the WT dimer, supporting the hypothesis that the N-terminal tails in the isolated dimer adopt a collapsed structure. (4) Electrostatic repulsion in the N-terminal tails decreases the stability of the H2A-H2B dimer.