Department of Molecular Biology, Cell Biology & Biochemistry, Brown University, Providence, RI 02903, USA.
Graduate Program in Therapeutic Sciences, Brown University, Providence, RI 02903, USA.
Biomolecules. 2023 Jan 31;13(2):264. doi: 10.3390/biom13020264.
The discovery of protein inhibitors of CRISPR-Cas systems, called anti-CRISPRs (Acrs), has enabled the development of highly controllable and precise CRISPR-Cas tools. Anti-CRISPRs share very little structural or sequential resemblance to each other or to other proteins, which raises intriguing questions regarding their modes of action. Many structure-function studies have shed light on the mechanism(s) of Acrs, which can act as orthosteric or allosteric inhibitors of CRISPR-Cas machinery, as well as enzymes that irreversibly modify CRISPR-Cas components. Only recently has the breadth of diversity of Acr structures and functions come to light, and this remains a rapidly evolving field. Here, we draw attention to a plethora of Acr mechanisms, with particular focus on how their action toward Cas proteins modulates conformation, dynamic (allosteric) signaling, nucleic acid binding, and cleavage ability.
CRISPR-Cas 系统的蛋白抑制剂（称为抗 CRISPRs，Acrs）的发现，使高度可控和精确的 CRISPR-Cas 工具得以开发。Acrs 彼此之间以及与其他蛋白质在结构或序列上几乎没有相似之处，这就提出了关于它们作用模式的有趣问题。许多结构功能研究阐明了 Acrs 的作用机制，它们可以作为 CRISPR-Cas 机制的正构或别构抑制剂，以及不可逆修饰 CRISPR-Cas 成分的酶。最近才发现 Acr 结构和功能的多样性，这仍然是一个快速发展的领域。在这里，我们提请注意大量的 Acr 机制，特别关注它们对 Cas 蛋白的作用如何调节构象、动态（别构）信号、核酸结合和切割能力。
