Back to Search
Start Over
Structural analyses unravel the molecular mechanism of cyclic di-GMP regulation of bacterial chemotaxis via a PilZ adaptor protein
- Publication Year :
- 2018
-
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. ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Published version
- Subjects :
- 0301 basic medicine
Cyclic di-GMP
Models, Molecular
Protein Conformation
Plasma protein binding
Biology
Flagellum
Crystallography, X-Ray
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Protein structure
Bacterial Proteins
Humans
Pseudomonas Infections
Molecular Biology
Cyclic GMP
030102 biochemistry & molecular biology
Chemotaxis
Signal transducing adaptor protein
Cell Biology
Cell biology
030104 developmental biology
chemistry
Flagella
Second messenger system
Pseudomonas aeruginosa
Crystal Structure
Function (biology)
Protein Binding
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....d295727b4f00eed0c6e5ef9bb5a3839d