Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/87353
Title: Structural analyses unravel the molecular mechanism of cyclic di-GMP regulation of bacterial chemotaxis via a PilZ adaptor protein
Authors: Yan, Xin-Fu
Xin, Lingyi
Yen, Jackie Tan
Zeng, Yukai
Jin, Shengyang
Cheang, Qing Wei
Fong, Rachel Andrea Chea Yuen
Chiam, Keng-Hwee
Liang, Zhao-Xun
Gao, Yong-Gui
Keywords: Chemotaxis
Crystal Structure
Issue Date: 2018
Source: Yan, X. F., Xin, L., Yen, J. T., Zeng, Y., Jin, S., Cheang, Q. W., et al. (2018). Structural analyses unravel the molecular mechanism of cyclic di-GMP regulation of bacterial chemotaxis via a PilZ adaptor protein. Journal of Biological Chemistry, 293(1), 100-111.
Series/Report no.: Journal of Biological Chemistry
Abstract: The bacterial second messenger cyclic di-GMP (c-di-GMP) has emerged as a prominent mediator of bacterial physiology, motility, and pathogenicity. c-di-GMP often regulates the function of its protein targets through a unique mechanism that involves a discrete PilZ adaptor protein. However, the molecular mechanism for PilZ protein–mediated protein regulation is unclear. Here, we present the structure of the PilZ adaptor protein MapZ cocrystallized in complex with c-di-GMP and its protein target CheR1, a chemotaxis-regulating methyltransferase in Pseudomonas aeruginosa. This cocrystal structure, together with the structure of free CheR1, revealed that the binding of c-di-GMP induces dramatic structural changes in MapZ that are crucial for CheR1 binding. Importantly, we found that restructuring and repositioning of two C-terminal helices enable MapZ to disrupt the CheR1 active site by dislodging a structural domain. The crystallographic observations are reinforced by protein–protein binding and single cell–based flagellar motor switching analyses. Our studies further suggest that the regulation of chemotaxis by c-di-GMP through MapZ orthologs/homologs is widespread in proteobacteria and that the use of allosterically regulated C-terminal motifs could be a common mechanism for PilZ adaptor proteins. Together, the findings provide detailed structural insights into how c-di-GMP controls the activity of an enzyme target indirectly through a PilZ adaptor protein.
URI: https://hdl.handle.net/10356/87353
http://hdl.handle.net/10220/44396
ISSN: 0021-9258
DOI: 10.1074/jbc.M117.815704
Rights: This research was originally published in the Journal of Biological Chemistry. © 2018 The American Society for Biochemistry and Molecular Biology. The published version is available at: [http://dx.doi.org/10.1074/jbc.M117.815704]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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