| Structural highlights
Function
[CHER1_PSEAE] Methylation of the membrane-bound methyl-accepting chemotaxis proteins (MCP) to form gamma-glutamyl methyl ester residues in MCP. [CDGBP_PSEAE] Binds the second messenger bis-(3'-5') cyclic dimeric guanosine monophosphate (c-di-GMP). Can bind two c-di-GMP molecules per monomer. May play a role in bacterial second-messenger regulated processes. Binding to c-di-GMP induces a conformational change of the C- and N-termini resulting in the exposure of a highly negative surface on one side of the protein to a possible effector protein.[1] [2] [3]
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ramelot TA, Yee A, Cort JR, Semesi A, Arrowsmith CH, Kennedy MA. NMR structure and binding studies confirm that PA4608 from Pseudomonas aeruginosa is a PilZ domain and a c-di-GMP binding protein. Proteins. 2007 Feb 1;66(2):266-71. PMID:17096419 doi:10.1002/prot.21199
- ↑ Shin JS, Ryu KS, Ko J, Lee A, Choi BS. Structural characterization reveals that a PilZ domain protein undergoes substantial conformational change upon binding to cyclic dimeric guanosine monophosphate. Protein Sci. 2011 Feb;20(2):270-7. doi: 10.1002/pro.557. Epub 2010 Dec 23. PMID:21280119 doi:http://dx.doi.org/10.1002/pro.557
- ↑ Habazettl J, Allan MG, Jenal U, Grzesiek S. Solution structure of the PilZ domain protein PA4608 complex with c-di-GMP identifies charge clustering as molecular readout. J Biol Chem. 2011 Feb 10. PMID:21310957 doi:10.1074/jbc.M110.209007
- ↑ Yan XF, Xin L, Yen JT, Zeng Y, Jin S, Cheang QW, Fong RACY, Chiam KH, Liang ZX, Gao YG. Structural Analyses Unravel the Molecular Mechanism of Cyclic di-GMP Regulation of Bacterial Chemotaxis via a PilZ Adaptor Protein. J Biol Chem. 2017 Nov 16. pii: M117.815704. doi: 10.1074/jbc.M117.815704. PMID:29146598 doi:http://dx.doi.org/10.1074/jbc.M117.815704
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