STRUCTURAL STUDY OF DISEASE RELATED FACTORS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们专注于各种胞苷脱氨酶，包括抗病毒蛋白APOBEC 3G和作用于tRNA的腺苷脱氨酶。所有典型的转运RNA（tRNA）在第8位都有一个尿苷，参与维持tRNA的三级结构。然而，极端嗜热古菌Methanopyrus kandleri在34个tRNA基因中有30个在第8位带有胞苷。我们证明了在这个位置的tRNA的三级核心的C-到-U编辑，并提出了一个tRNA特异性的胞苷脱氨酶，CDAT 8，它具有连接到一个tRNA结合THUMP域的胞苷脱氨酶域的晶体结构。CDAT 8对位置8处的C脱氨基具有特异性，仅需要受体茎发夹来进行活性，并且属于“胞苷脱氨酶”中的独特家族就像”超级家庭。这种C-to-U编辑酶的存在促进了所有M的正确折叠和功能。坎德莱里转移RNA。我们还研究了硫磺素T检测淀粉样蛋白的机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We focus on various cytidine deaminases, including the antiviral protein APOBEC3G and adenosine deaminases acting on tRNA. All canonical transfer RNAs (tRNAs) have a uridine at position 8, involved in maintaining tRNA tertiary structure. However, the hyperthermophilic archaeon Methanopyrus kandleri harbors 30 (out of 34) tRNA genes with cytidine at position 8. We demonstrate C-to-U editing at this location in the tRNA's tertiary core, and present the crystal structure of a tRNA-specific cytidine deaminase, CDAT8, which has the cytidine deaminase domain linked to a tRNA-binding THUMP domain. CDAT8 is specific for C deamination at position 8, requires only the acceptor stem hairpin for activity, and belongs to a unique family within the "cytidine deaminaselike" superfamily. The presence of this C-to-U editing enzyme facilitates the proper folding and functionality of all M. kandleri tRNAs. We also work on the mechanism of amyloid detection by Thioflavin T.