Cyclic di-AMP, a second messenger of primary importance: tertiary structures and binding mechanisms
Cyclic di-AMP, a second messenger of primary importance: tertiary structures and binding mechanisms
复制标题
环状二-AMP，最重要的第二信使：三级结构和结合机制
DOI：
10.1093/nar/gkaa112
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发表时间：
2020-04-06
影响因子：
14.9
通讯作者：
Chou, Shan-Ho
中科院分区：
文献类型：
--
作者：
He, Jin;Yin, Wen;Chou, Shan-Ho
环二腺苷酸（c-di-AMP）是细菌和古细菌中广泛存在的第二信使，其参与维持渗透压、响应DNA损伤、控制中枢代谢、生物膜形成、抗酸胁迫和其他功能。c-di AMP的主要重要性源于其在标准生长条件下对许多细菌的重要性以及几种真核蛋白质感测其在细胞质中的存在并引发宿主细胞的免疫应答的能力。我们在这里审查的三级结构的域，调节c-di-AMP的合成和信号，和c-di-AMP的结合机制，包括在各种晶体结构中观察到的c-di-AMR的主要构象。我们讨论了这些c-di-AMP分子是如何与蛋白质和核糖开关受体结合的，以及什么样的相互作用导致了c-di-AMP配体的特异性高亲和力结合。本文描述了c-di-AMP与其受体蛋白之间的七种非共价π相互作用，包括π-π、C-H-π、阳离子极性π、疏水π、阴离子π和孤对π相互作用。我们还比较了c-di-AMP和c-di-GMP各自受体的结合机制，这些受体允许这两种环状二核苷酸控制非常不同的生物学功能。
Cyclic diadenylate (c-di-AMP) is a widespread second messenger in bacteria and archaea that is involved in the maintenance of osmotic pressure, response to DNA damage, and control of central metabolism, biofilm formation, acid stress resistance, and other functions. The primary importance of c-di AMP stems from its essentiality for many bacteria under standard growth conditions and the ability of several eukaryotic proteins to sense its presence in the cell cytoplasm and trigger an immune response by the host cells. We review here the tertiary structures of the domains that regulate c-di-AMP synthesis and signaling, and the mechanisms of c-di-AMP binding, including the principal conformations of c-di-AMR observed in various crystal structures. We discuss how these c-di-AMP molecules are bound to the protein and riboswitch receptors and what kinds of interactions account for the specific high-affinity binding of the c-di-AMP ligand. We describe seven kinds of non-covalent-pi; interactions between c-di-AMP and its receptor proteins, including pi-pi, C-H-pi, cation polar-pi, hydrophobic-pi, anion-pi and the lone pair--pi interactions. We also compare the mechanisms of c-di-AMP and c-di-GMP binding by the respective receptors that allow these two cyclic dinucleotides to control very different biological functions.