a Department of Molecular Biology and Biochemistry , University of California Irvine , Irvine , CA , USA.
b Department of Pharmaceutical Sciences , University of California Irvine , Irvine , CA , USA.
RNA Biol. 2018 Jan 2;15(1):9-12. doi: 10.1080/15476286.2017.1387710. Epub 2017 Nov 21.
Bovine pancreatic ribonuclease (RNase A) is the founding member of the RNase A superfamily. Members of this superfamily of ribonucleases have high sequence diversity, but possess a similar structural fold, together with a conserved His-Lys-His catalytic triad and structural disulfide bonds. Until recently, RNase A proteins had exclusively been identified in eukaryotes within vertebrae. Here, we discuss the discovery by Batot et al. of a bacterial RNase A superfamily member, CdiA-CT: a toxin that belongs to an inter-bacterial competition system from Yersinia kristensenii. CdiA-CT exhibits the same structural fold as conventional RNase A family members and displays in vitro and in vivo ribonuclease activity. However, CdiA-CT shares little to no sequence similarity with RNase A, and lacks the conserved disulfide bonds and catalytic triad of RNase A. Interestingly, the CdiA-CT active site more closely resembles the active site composition of various eukaryotic endonucleases. Despite lacking sequence similarity to eukaryotic RNase A family members, CdiA-CT does share high sequence similarity with numerous Gram-negative and Gram-positive bacterial proteins/domains. Nearly all of these bacterial homologs are toxins associated with virulence and bacterial competition, suggesting that the RNase A superfamily has a distinct bacterial subfamily branch, which likely arose by way of convergent evolution. Finally, RNase A interacts directly with the immunity protein of CdiA-CT, thus the cognate immunity protein for the bacterial RNase A member could be engineered as a new eukaryotic RNase A inhibitor.
牛胰核糖核酸酶（RNase A）是核糖核酸酶 A 超家族的创始成员。该超家族的核糖核酸酶具有高度的序列多样性，但具有相似的结构折叠，以及保守的 His-Lys-His 催化三联体和结构二硫键。直到最近，RNase A 蛋白才仅在脊椎动物中的真核生物中被识别。在这里，我们讨论了 Batot 等人的发现，即细菌 RNase A 超家族成员 CdiA-CT：一种来自耶尔森氏菌的细菌间竞争系统的毒素。CdiA-CT 表现出与传统 RNase A 家族成员相同的结构折叠，并显示体外和体内核糖核酸酶活性。然而，CdiA-CT 与 RNase A 的序列相似性很小，并且缺乏 RNase A 的保守二硫键和催化三联体。有趣的是，CdiA-CT 的活性位点更类似于各种真核内切核酸酶的活性位点组成。尽管与真核 RNase A 家族成员缺乏序列相似性，但 CdiA-CT 与许多革兰氏阴性和革兰氏阳性细菌蛋白/结构域具有高度序列相似性。几乎所有这些细菌同源物都是与毒力和细菌竞争相关的毒素，这表明 RNase A 超家族具有独特的细菌亚家族分支，这可能是通过趋同进化产生的。最后，RNase A 与 CdiA-CT 的免疫蛋白直接相互作用，因此细菌 RNase A 成员的同源免疫蛋白可以被设计为新型的真核 RNase A 抑制剂。
