Structural basis for the regulation of chemotaxis by MapZ in the presence of c-di-GMP

Zhu, Y.; Yuan, Zenglin; Gu, Lichuan

doi:10.1107/s2059798317009998

Cited by 9 publications

(7 citation statements)

References 27 publications

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“…Structural superposition of PilZ domains from K. xylinus AcsAB, P. aeruginosa Alg44 and C-terminal domains of E. coli YcgR, V. cholerae PlzD, and K. pneumoniae MrkH against the high-resolution structure of the PilZ domain protein MapZ (PA4608) of P. aeruginosa (24, 26, 40) is shown in Fig. 1, while pairwise superpositions of the domains listed in Table 1 are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

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Structural conservation and diversity of PilZ-related domains

Galperin

Chou

2019

Preprint

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The widespread bacterial second messenger cyclic diguanylate (c-di-GMP) regulates a 1 variety of processes, including protein secretion, motility, cell development, and biofilm 2 formation. C-di-GMP-dependent responses are often mediated by its binding to the 3 cytoplasmic receptors that contain the PilZ domain. We present here comparative 4 structural and sequence analysis of various PilZ-related domains and describe three 5 principal types of them: (i) the canonical PilZ domain, whose structure includes a six-6 stranded beta-barrel and a C-terminal alpha-helix; (ii) an atypical PilZ domain that 7 contains two extra alpha-helices and forms stable tetramers, and (iii) divergent PilZ-8 related domains, which include the eponymous PilZ protein and PilZN (YcgR_N) and 9 PilZNR (YcgR_2) domains. We refine the second c-di-GMP binding motif of PilZ as 10 [D/N]hSxxG and show that the hydrophobic residue h of this motif interacts with a cluster 11 of conserved hydrophobic residues, helping maintain the PilZ domain fold. We describe 12 several novel PilZN-type domains that are fused to the canonical PilZ domains in specific 13 taxa, such as spirochetes, actinobacteria, cellulosolytic clostridia, deltaproteobacteria, 14 and aquificae. We propose that the evolution of three major groups of PilZ domains 15 included (i) fusion of pilZ with other genes, which produced Alg44, cellulose synthase, and 16 other multidomain proteins; (ii) insertion of a ~200-bp fragment, which resulted in the 17 formation of tetramer-forming PilZ proteins, and (iii) tandem duplication of pilZ genes, 18 which led to the formation of PilZ dimers and YcgR-like proteins. 19 IMPORTANCE 20Cyclic di-GMP is a ubiquitous bacterial second messenger that regulates motility, biofilm 21 formation and virulence of many bacterial pathogens. The PilZ domain is a widespread c-22 di-GMP receptor that binds c-di-GMP through its RxxxR and [D/N]xSxxG motifs; some PilZ 23 domains lack these motifs and are unable to bind c-di-GMP. We used structural and 24 sequence analysis to assess the diversity of PilZ-related domains and define their common 25 features. We show that the hydrophobic residue h in the second motif is highly conserved; 26 it may serve as a readout for c-di-GMP binding. We describe three principal classes of 27 PilZ-related domains: canonical, tetramer-forming, and divergent PilZ domains, and 28 propose the evolutionary pathways that led to the emergence of these PilZ types. 29 30

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Section: Resultsmentioning

confidence: 99%

“…Over the years, structures of several PilZ domains and PilZ-containing proteins have been solved (22, 24, 25, 34-40), providing valuable insight into the mechanisms of c-di-GMP binding and the roles of the conserved RxxxR and [D/N]xSxxG c-di-GMP-binding motifs (reviewed in ref. 9 and 10).…”

Section: Introductionmentioning

confidence: 99%

Structural conservation and diversity of PilZ-related domains

Galperin

Chou

2019

Preprint

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“…Within this cluster is MapZ, a single-domain PilZ protein from P. aeruginosa PAO1. MapZ is one of the best characterized PilZ proteins with its structure, interacting partner and physiological function elucidated 5,[31][32][33][34] . In vitro and in vivo studies revealed that MapZ binds c-di-GMP with a KD in the range of 6-9 µM 5, 32 , and that it interacts with the chemotaxis methyltransferase CheR1 at elevated c-di-GMP concentrations.…”

Section: A Large Group Of Single-domain Pilz Proteins Predicted To Inmentioning

confidence: 99%

“…In vitro and in vivo studies revealed that MapZ binds c-di-GMP with a KD in the range of 6-9 µM 5, 32 , and that it interacts with the chemotaxis methyltransferase CheR1 at elevated c-di-GMP concentrations. Crystallographic studies on the MapZ/CheR1/c-di-GMP ternary complex identified that the two C-terminal helices α1 (residues 92-106aa) and α2 (residues 109-121) of MapZ are the key motifs mediating MapZ-CheR1 interaction ( Figure 6C) 7,33 . In particular, the helix α1 plays an essential role in mediating the MapZ-CheR1 interaction by occupying the central cleft of CheR1.…”

Section: A Large Group Of Single-domain Pilz Proteins Predicted To Inmentioning

confidence: 99%

Large-scale sequence similarity analysis reveals the scope of sequence and function divergence in PilZ domain proteins

Cheang

Sheng

et al. 2020

Preprint

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PilZ domain-containing proteins constitute a superfamily of widely distributed bacterial signalling proteins. Although studies have established the canonical PilZ domain as an adaptor protein domain evolved to specifically bind the second messenger c-di-GMP, mounting evidence suggest that the PilZ domain has undergone enormous divergent evolution to generate a superfamily of proteins that are characterized by a wide range of c-di-GMP-binding affinity, binding partners and cellular functions. The divergent evolution has even generated families of non-canonical PilZ domains that completely lack c-di-GMP binding ability. In this study, we performed a large-scale sequence analysis on more than 28,000 single-and di-domain PilZ proteins using the sequence similarity networking tool created originally to analyse functionally diverse enzyme superfamilies. The sequence similarity networks (SSN) generated by the analysis feature a large number of putative isofunctional protein clusters, and thus, provide an unprecedented panoramic view of the sequence-function relationship and function diversification in PilZ proteins. Some of the protein clusters in the networks are considered as unexplored clusters that contain proteins with completely unknown biological function;whereas others contain one, two or a few functionally known proteins, and therefore, enabling us to infer the cellular function of uncharacterized homologs or orthologs. With the ultimate goal of elucidating the diverse roles played by PilZ proteins in bacterial signal transduction, the work described here will facilitate the annotation of the vast number of PilZ proteins encoded by bacterial genome and help to prioritize functionally unknown PilZ proteins for future studies.3 Importance Although PilZ domain is best known as the protein domain evolved specifically for the binding of the second messenger c-di-GMP, divergent evolution has generated a superfamily of PilZ proteins with a diversity of ligand or protein-binding properties and cellular functions.We analysed the sequences of more than 28,000 PilZ proteins using the sequence similarity networking (SSN) tool to yield a global view of the sequence-function relationship and function diversification in PilZ proteins. The results will facilitate the annotation of the vast number of PilZ proteins encoded by bacterial genomes and help us prioritize PilZ proteins for future studies.

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“…Structural superposition of PilZ domains from K. xylinus AcsAB and P. aeruginosa Alg44 and C-terminal domains of E. coli YcgR, V. cholerae PlzD, and K. pneumoniae MrkH against the high-resolution structure of the PilZ domain protein MapZ (PA4608) of P. aeruginosa (24,26,42) is shown in Fig. 1, while pairwise superpositions of the domains listed in Table 1 are shown in Fig.…”

mentioning

confidence: 99%

Structural Conservation and Diversity of PilZ-Related Domains

Galperin

Chou

2020

J Bacteriol

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The widespread bacterial second messenger cyclic diguanylate (c-di-GMP) regulates a variety of processes, including protein secretion, motility, cell development, and biofilm formation. c-di-GMP-dependent responses are often mediated by its binding to the cytoplasmic receptors that contain the PilZ domain. Here, we present comparative structural and sequence analysis of various PilZ-related domains and describe three principal types of them: (i) the canonical PilZ domain, whose structure includes a six-stranded beta-barrel and a C-terminal alpha helix, (ii) an atypical PilZ domain that contains two extra alpha helices and forms stable tetramers, and (iii) divergent PilZ-related domains, which include the eponymous PilZ protein and PilZN (YcgR_N) and PilZNR (YcgR_2) domains. We refine the second c-di-GMP binding motif of PilZ as [D/N]hSXXG and show that the hydrophobic residue h of this motif interacts with a cluster of conserved hydrophobic residues, helping maintain the PilZ domain fold. We describe several novel PilZN-type domains that are fused to the canonical PilZ domains in specific taxa, such as spirochetes, actinobacteria, aquificae, cellulose-degrading clostridia, and deltaproteobacteria. We propose that the evolution of the three major groups of PilZ domains included (i) fusion of pilZ with other genes, which produced Alg44, cellulose synthase, and other multidomain proteins; (ii) insertion of an ϳ200-bp fragment, which resulted in the formation of tetramer-forming PilZ proteins; and (iii) tandem duplication of pilZ genes, which led to the formation of PilZ dimers and YcgR-like proteins. IMPORTANCE c-di-GMP is a ubiquitous bacterial second messenger that regulates motility, biofilm formation, and virulence of many bacterial pathogens. The PilZ domain is a widespread c-di-GMP receptor that binds c-di-GMP through its RXXXR and [D/N]hSXXG motifs; some PilZ domains lack these motifs and are unable to bind c-di-GMP. We used structural and sequence analysis to assess the diversity of PilZ-related domains and define their common features. We show that the hydrophobic residue h in the second position of the second motif is highly conserved; it may serve as a readout for c-di-GMP binding. We describe three principal classes of PilZ-related domains, canonical, tetramer-forming, and divergent PilZ domains, and propose the evolutionary pathways that led to the emergence of these PilZ types.

show abstract

Structural basis for the regulation of chemotaxis by MapZ in the presence of c-di-GMP

Cited by 9 publications

References 27 publications

Structural conservation and diversity of PilZ-related domains

Structural conservation and diversity of PilZ-related domains

Large-scale sequence similarity analysis reveals the scope of sequence and function divergence in PilZ domain proteins

Structural Conservation and Diversity of PilZ-Related Domains

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