Tied up in knots: Untangling substrate recognition by the SPOUT methyltransferases.
Tied up in knots: Untangling substrate recognition by the SPOUT methyltransferases.
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DOI：
10.1016/j.jbc.2022.102393
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发表时间：
2022-10
影响因子：
4.8
通讯作者：
Conn, Graeme L.
中科院分区：
文献类型：
--
作者：
Strassler, Sarah E.;Bowles, Isobel E.;Dey, Debayan;Jackman, Jane E.;Conn, Graeme L.
当转移 RNA 修饰酶 TrmH (SpoU) 和 TrmD 之间的结构相似性被鉴定时，SpoU-TrmD (SPOUT) 甲基转移酶超家族被指定。 SPOUT 甲基转移酶存在于生命的所有领域，主要修饰转移 RNA 或核糖体 RNA 底物，尽管已经报道了一种具有蛋白质底物的酶的实例。 SPOUT 甲基转移酶进行的修饰在调节细胞过程中发挥着多种作用，例如确保翻译保真度、改变 RNA 稳定性以及赋予细菌对抗生素的耐药性。这一大量 S-腺苷-L-甲硫氨酸依赖性甲基转移酶由独特的 α/β 折叠定义，其催化 (SPOUT) 结构域中具有深三叶结。在此，我们描述了 SPOUT 酶结构、结构域结构和催化功能关键要素（包括 S-腺苷-L-甲硫氨酸共底物结合）的当前知识，从将 SPOUT 甲基转移酶超家族分为四个主要分支的新序列比对开始。最后，本综述的一个主要焦点将是我们对这些不同的酶如何完成特定底物识别和修饰的分子壮举的日益了解，正如我们对蛋白质-RNA复合物结构的了解的最新进展以及发现一种 SPOUT 甲基转移酶对金属离子结合催化的依赖性所强调的那样。考虑到 RNA 修饰的广泛生物学作用，深入了解 SPOUT 酶的底物识别过程对于定义与人类疾病相关的基本 RNA 生物学的许多方面至关重要。
The SpoU-TrmD (SPOUT) methyltransferase superfamily was designated when structural similarity was identified between the transfer RNA–modifying enzymes TrmH (SpoU) and TrmD. SPOUT methyltransferases are found in all domains of life and predominantly modify transfer RNA or ribosomal RNA substrates, though one instance of an enzyme with a protein substrate has been reported. Modifications placed by SPOUT methyltransferases play diverse roles in regulating cellular processes such as ensuring translational fidelity, altering RNA stability, and conferring bacterial resistance to antibiotics. This large collection of S-adenosyl-L-methionine-dependent methyltransferases is defined by a unique α/β fold with a deep trefoil knot in their catalytic (SPOUT) domain. Herein, we describe current knowledge of SPOUT enzyme structure, domain architecture, and key elements of catalytic function, including S-adenosyl-L-methionine co-substrate binding, beginning with a new sequence alignment that divides the SPOUT methyltransferase superfamily into four major clades. Finally, a major focus of this review will be on our growing understanding of how these diverse enzymes accomplish the molecular feat of specific substrate recognition and modification, as highlighted by recent advances in our knowledge of protein–RNA complex structures and the discovery of the dependence of one SPOUT methyltransferase on metal ion binding for catalysis. Considering the broad biological roles of RNA modifications, developing a deeper understanding of the process of substrate recognition by the SPOUT enzymes will be critical for defining many facets of fundamental RNA biology with implications for human disease.
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