Binding site profiles and N-terminal minor groove interactions of the master quorum-sensing regulator LuxR enable flexible control of gene activation and repression.
Binding site profiles and N-terminal minor groove interactions of the master quorum-sensing regulator LuxR enable flexible control of gene activation and repression.
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主群体感应调节因子 LuxR 的结合位点分布和 N 端小沟相互作用能够灵活控制基因激活和抑制
DOI：
10.1093/nar/gkab150
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发表时间：
2021-04-06
影响因子：
14.9
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Zhang J;Liu B;Gu D;Hao Y;Chen M;Ma Y;Zhou X;Reverter D;Zhang Y;Wang Q
摘要LuxR是TetR家族中的一个群体感应（QS）调节因子，激活或抑制数百个控制弧菌群体行为的基因的表达，其机制尚不清楚。为了阐明这种调节剂如何控制各种靶基因的表达，我们应用了ChIP-seq和DNase I-seq技术。溶藻弧菌LuxR控制含有对称回文（repDNA）或不对称（actDNA）结合基序的280个基因的表达，这些基序具有不同的结合特征。激活基因的LuxR结合位点的中位数几乎是抑制基因的两倍。与各自的repDNA和actDNA基序复合的LuxR的晶体结构揭示了一种新的LuxR DNA结合模式，该模式涉及其N-末端延伸与小沟的接触。当LuxR结合repDNA与actDNA时，精氨酸-9和精氨酸-11介导的N-末端接触不同，导致在被抑制的靶标处具有更高的结合亲和力。此外，修饰LuxR结合位点、结合特征和N-末端延伸对QS调节的表型具有重要影响。这些结果有助于从根本上理解弧菌QS中LuxR控制基因激活和抑制的机制的高度灵活性，这可能有助于设计QS抑制化学物质，干扰LuxR调节，以有效地控制病原体。
Abstract LuxR is a TetR family master quorum sensing (QS) regulator activating or repressing expression of hundreds of genes that control collective behaviors in Vibrios with underlying mechanism unknown. To illuminate how this regulator controls expression of various target genes, we applied ChIP-seq and DNase I-seq technologies. Vibrio alginolyticus LuxR controls expression of ∼280 genes that contain either symmetric palindrome (repDNA) or asymmetric (actDNA) binding motifs with different binding profiles. The median number of LuxR binding sites for activated genes are nearly double for that of repressed genes. Crystal structures of LuxR in complex with the respective repDNA and actDNA motifs revealed a new mode of LuxR DNA binding that involves contacts of its N-terminal extension to the minor groove. The N-terminal contacts mediated by Arginine-9 and Arginine-11 differ when LuxR binds to repDNA vs actDNA, leading to higher binding affinity at repressed targets. Moreover, modification of LuxR binding sites, binding profiles, and N-terminal extension have important consequences on QS-regulated phenotypes. These results facilitate fundamental understanding of the high flexibility of mechanisms of LuxR control of gene activation and repression in Vibrio QS, which may facilitate to design QS inhibiting chemicals that interfere with LuxR regulation to effectively control pathogens.
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影响因子：
8.4
作者：
Bagert JD;van Kessel JC;Sweredoski MJ;Feng L;Hess S;Bassler BL;Tirrell DA
通讯作者：
Tirrell DA
影响因子：
6.4
作者：
Lee KJ;Jung YC;Park SJ;Lee KH
通讯作者：
Lee KH
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
sigma(E) 介导的温度计控制溶藻弧菌从 LuxR 介导的毒力基因表达到热应激适应的转变
影响因子：
6.7
作者：
Gu D;Guo M;Yang M;Zhang Y;Zhou X;Wang Q
通讯作者：
Wang Q
影响因子：
3.2
作者：
Henke, JM;Bassler, BL
通讯作者：
Bassler, BL