Structural analyses unravel the molecular mechanism of cyclic di-GMP regulation of bacterial chemotaxis via a PilZ adaptor protein

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Structural analyses unravel the molecular mechanism of cyclic di-GMP regulation of bacterial chemotaxis via a PilZ adaptor protein
Title:
Structural analyses unravel the molecular mechanism of cyclic di-GMP regulation of bacterial chemotaxis via a PilZ adaptor protein
Other Titles:
Journal of Biological Chemistry
Publication Date:
16 November 2017
Citation:
Yan, X.-F., Xin, L., Yen, J. T., Zeng, Y., Jin, S., Cheang, Q. W., … Gao, Y.-G. (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. doi:10.1074/jbc.m117.815704
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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This work was supported by Ministry of Education of Singapore Tier I Grants RG40/17 (to Z.-X. L.) and RG43/15 (to Y.-G. G.). The authors declare that they have no conflicts of interest with the contents of this article.
Description:
ISSN:
1083-351X
0021-9258
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