The structure of Deinococcus radiodurans transcriptional regulator HucR retold with the urate bound
The structure of Deinococcus radiodurans transcriptional regulator HucR retold with the urate bound
复制标题
耐辐射奇球菌转录调节因子 HucR 的结构与尿酸盐结合重述
DOI：
10.1016/j.bbrc.2022.05.034
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发表时间：
2022
影响因子：
3.1
通讯作者：
Wilkinson, Steven P.
中科院分区：
文献类型：
--
作者：
Rho, SooHo;Jung, WeonSeok;Park, Jeong Kuk;Choi, Min Hee;Kim, MinJu;Kim, JooYoung;Byun, JiWon;Park, Taehyun;Lee, Byung Il;Wilkinson, Steven P.
HucR是Deinococcus radiodurans的一个马尔R家族蛋白，它与HucR基因间区和尿酸酶基因紧密结合，抑制它们的表达。尿酸盐（或尿酸）通过与HucR结合以阻止其与同源DNA结合来拮抗HucR的阻遏物功能。先前报道的HucR的晶体结构没有结合的尿酸盐，显示出与其他马尔R结构的显著结构同源性。本文报道了用尿酸盐键测定HucR的晶体结构。然而，尽管事实上发现尿酸盐存在于其他马尔家族蛋白中众所周知的含有配体的位点，但总体HucR结构表明结合尿酸盐后结构没有发生显著变化。结构分析进一步表明HucR中的尿酸盐相互作用由组氨酸/谷氨酸侧链和由各种残基稳定的有序水分子介导。这种相互作用是非常独特的相比，其他已知的结构之间的相互作用尿酸盐和它的结合蛋白。此外，载脂蛋白和尿酸盐结合形式的结构比较允许我们假设，载脂蛋白形式中的Trp 20介导的水网络稳定了同源DNA结合的适当HucR折叠，并且尿酸盐结合，也通过Trp 20，以及随后的结合口袋中水分子的重组，可能破坏DNA结合构型，导致DNA结合减弱。
HucR is a MarR family protein ofDeinococcus radiodurans, which binds tightly to the intergenic region ofHucRand the uricase gene to inhibit their expression. Urate (or uric acid) antagonizes the repressor function of HucR by binding to HucR to impede its association with the cognate DNA. The previously reported crystal structure of HucR was without the bound urate showing significant structural homology to other MarR structures. In this paper, we report the crystal structure of HucR determined with the urate bound. However, despite the fact that the urate is found at a site well-known to harbor ligands in other MarR family proteins, the overall HucR structure indicates that no significant change in structure takes place with the urate bound. Structure analysis further suggests that the urate interaction in HucR is mediated by histidine/glutamate side chains and ordered water molecules stabilized by various residues. Such interaction is quite unique compared to other known structural interactions between urate and its binding proteins. Furthermore, structural comparison of the apo- and the urate bound forms allows us to hypothesize that the Trp20-mediated water network in the apo-form stabilizes the proper HucR fold for cognate DNA binding, and that urate binding, alsoviaTrp20, and the consequent reorganization of water molecules in the binding pocket, likely disrupts the DNA binding configuration to result in the attenuated DNA binding.