Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, USA.
Curr Opin Struct Biol. 2024 Dec;89:102921. doi: 10.1016/j.sbi.2024.102921. Epub 2024 Sep 17.
Chromatin is a complex of DNA with histone proteins organized into nucleosomes that regulates genome accessibility and controls transcription, replication and repair by dynamically switching between open and compact states as a function of different parameters including histone post-translational modifications and interactions with chromatin modulators. Continuing advances in structural biology techniques including X-ray crystallography, cryo-electron microscopy and nuclear magnetic resonance (NMR) spectroscopy have facilitated studies of chromatin systems, in spite of challenges posed by their large size and dynamic nature, yielding important functional and mechanistic insights. In this review we highlight recent applications of magic angle spinning solid-state NMR - an emerging technique that is uniquely-suited toward providing atomistic information for rigid and flexible regions within biomacromolecular assemblies - to detailed characterization of structure, conformational dynamics and interactions for histone core and tail domains in condensed nucleosomes and oligonucleosome arrays mimicking chromatin at high densities characteristic of the cellular environment.
染色质是由 DNA 与组蛋白组成的复合物,这些组蛋白形成核小体,通过在不同参数(包括组蛋白翻译后修饰和与染色质调节剂的相互作用)之间动态切换,在开放和紧凑状态之间转换,从而调节基因组的可及性,并控制转录、复制和修复。尽管受到其较大尺寸和动态性质的挑战,但包括 X 射线晶体学、冷冻电子显微镜和核磁共振(NMR)光谱学在内的结构生物学技术的不断进步,促进了对染色质系统的研究,为其提供了重要的功能和机制见解。在这篇综述中,我们重点介绍了魔角旋转固态 NMR 的最新应用——一种新兴技术,特别适合提供生物大分子组装体中刚性和柔性区域的原子信息——用于详细表征结构、构象动力学和相互作用在凝聚核小体和寡核小体阵列中的核心和尾部结构域,这些寡核小体阵列模拟了细胞环境中高浓度的染色质。