Binding site profiles and N-terminal minor groove interactions of the master quorum-sensing regulator LuxR enable flexible control of gene activation and repression
Zhang, Jun (East China University of Science and Technology. State Key Laboratory of Bioreactor Engineering (China))
Liu, Bing (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Gu, Dan (Yangzhou University. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses (China))
Hao, Yuan (East China University of Science and Technology. State Key Laboratory of Bioreactor Engineering (China))
Chen, Mo (East China University of Science and Technology. State Key Laboratory of Bioreactor Engineering (China))
Ma, Yue (East China University of Science and Technology. State Key Laboratory of Bioreactor Engineering (China))
Zhou, Xiaohui (University of Connecticut. Department of Pathobiology and Veterinary Science (USA))
Reverter i Cendrós, David (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Zhang, Yuanxing (Southern Marine Science and Engineering Guangdong Laboratory (China))
Wang, Qiyao (East China University of Science and Technology. State Key Laboratory of Bioreactor Engineering (China))
Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular

Data:	2021
Resum:	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.
Ajuts:	Ministerio de Ciencia e Innovación PGC2018-098423-B-I00
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Nucleic acids research, Vol. 49, Issue 6 (April 2021) , p. 3274-3293, ISSN 1362-4962

DOI: 10.1093/nar/gkab150
PMID: 33693882

20 p, 10.5 MB

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