5y4r

Publication Abstract from PubMed

The bacterial second messenger cyclic di-GMP (c-di-GMP) has emerged as a prominent mediator of bacterial physiology, motility and pathogenicity. Cdi-GMP often regulates the function of its protein targets through a unique mechanism that involves a discrete PilZ adaptor protein. However, the molecular mechanism in c-di-GMP-mediated protein regulation is unclear. Here, we present the structure of the PilZ adaptor protein MapZ co-crystallized in complex with c-di-GMP and its protein target CheR1, a chemotaxis-regulating methyltransferase in Pseudomonas aeruginosa This co-crystal 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 enables MapZ to disrupt the CheR1 active site by dislodging a structural domain. The crystallographic observations are reinforced by proteinprotein binding and single cell-based flagellar motor switching analysis. 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.

Structural Analyses Unravel the Molecular Mechanism of Cyclic di-GMP Regulation of Bacterial Chemotaxis via a PilZ Adaptor Protein.,Yan XF, Xin L, Yen JT, Zeng Y, Jin S, Cheang QW, Fong RACY, Chiam KH, Liang ZX, Gao YG J Biol Chem. 2017 Nov 16. pii: M117.815704. doi: 10.1074/jbc.M117.815704. PMID:29146598^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.