Diversity of structure and function of response regulator output domains

Abstract

Response regulators (RRs) within two-component signal transduction systems control a variety of cellular processes. Most RRs contain DNA-binding output domains and serve as transcriptional regulators. Other RR types contain RNA-binding, ligand-binding, protein-binding or transporter output domains and exert regulation at the transcriptional, post-transcriptional or post-translational levels. In a significant fraction of RRs, output domains are enzymes that themselves participate in signal transduction: methylesterases, adenylate or diguanylate cyclases, c-di-GMP-specific phosphodiesterases, histidine kinases, serine/threonine protein kinases and protein phosphatases. In addition, there remain output domains whose functions are still unknown. Patterns of the distribution of various RR families are generally conserved within key microbial lineages and can be used to trace adaptations of various species to their unique ecological niches.

Figure 1. Distribution of common output domains of bacterial response regulators

A. Aggregate data for all bacterial species. The sector for Fis domain includes response regulators of the NtrC and ActR families (no structure of a Fis-DNA complex is currently available). Unlabelled output domains (clockwise from AraC) are as follows: Spo0A (dark blue), ANTAR (cyan), CheW (pink), CheC (white), GGDEF+EAL (orange), HD-GYP (yellow). The domain structures are as in Tables 1 and 2 and are taken from Protein Data Bank in Europe [52]. B. Response regulator family profiles for selected bacterial phyla, Archaea, and α, β, γ and δ subdivisions of Proteobacteria. The columns indicate the relative fractions of the RRs of single-domain (white), OmpR (maroon), NarL (bisque), NtrC (blue), combined LytR, ActR, YesN/AraC, and Spo0A (purple), CheB (magenta), combined c-di-GMP signaling (WspR, PleD, PvrR, FimX, and RpfG, orange), and enzymatic (HisK and PP2C output domains, green) families within each taxonomic group. The grey bars indicate combined fractions of all other RR families.

Figure 1. Distribution of common output domains of bacterial response regulators

A. Aggregate data for all bacterial species. The sector for Fis domain includes response regulators of the NtrC and ActR families (no structure of a Fis-DNA complex is currently available). Unlabelled output domains (clockwise from AraC) are as follows: Spo0A (dark blue), ANTAR (cyan), CheW (pink), CheC (white), GGDEF+EAL (orange), HD-GYP (yellow). The domain structures are as in Tables 1 and 2 and are taken from Protein Data Bank in Europe [52]. B. Response regulator family profiles for selected bacterial phyla, Archaea, and α, β, γ and δ subdivisions of Proteobacteria. The columns indicate the relative fractions of the RRs of single-domain (white), OmpR (maroon), NarL (bisque), NtrC (blue), combined LytR, ActR, YesN/AraC, and Spo0A (purple), CheB (magenta), combined c-di-GMP signaling (WspR, PleD, PvrR, FimX, and RpfG, orange), and enzymatic (HisK and PP2C output domains, green) families within each taxonomic group. The grey bars indicate combined fractions of all other RR families.

Figure 2. Response regulator family profiles in representatives of the genus Shewanella (A) and the family Bacillaceae (B)

The columns indicate the number of response regulators of each family encoded in each genome. The family names as in Tables 1 and 2; the REC column shows the number of single-domain RRs (no output domains), the WspR column shows combined data for WspR and PleD families (the GGDEF output domain), the FimX label indicates response regulators that contain fused GGDEF and EAL output domains. The organisms (from front to back) are as follows (only every other row is labeled): A: Shewanella denitrificans OS217, S. frigidimarina NCIMB 400, S. halifaxensis HAW-EB4, S. pealeana ATCC 700345, S. baltica OS155, S. loihica PV-4, S. piezotolerans WP3, S. oneidensis MR-1, S. amazonensis SB2B, S. woodyi ATCC 51908, and S. sediminis HAW-EB3. B: Anoxybacillus flavithermus WK1, Geobacillus kaustophilus HTA426 G. thermodenitrificans NG80-2, Bacillus pumilus SAFR-032, B. subtilis subsp. subtilis str. 168, B. amyloliquefaciens FZB42, B. licheniformis ATCC 14580, B. clausii KSM-K16, B. cereus ATCC 14579, B. anthracis str. Ames, B. halodurans C-125, B. thuringiensis serovar konkukian str. 97–27, and B. weihenstephanensis KBAB4.

Figure 2. Response regulator family profiles in representatives of the genus Shewanella (A) and the family Bacillaceae (B)

The columns indicate the number of response regulators of each family encoded in each genome. The family names as in Tables 1 and 2; the REC column shows the number of single-domain RRs (no output domains), the WspR column shows combined data for WspR and PleD families (the GGDEF output domain), the FimX label indicates response regulators that contain fused GGDEF and EAL output domains. The organisms (from front to back) are as follows (only every other row is labeled): A: Shewanella denitrificans OS217, S. frigidimarina NCIMB 400, S. halifaxensis HAW-EB4, S. pealeana ATCC 700345, S. baltica OS155, S. loihica PV-4, S. piezotolerans WP3, S. oneidensis MR-1, S. amazonensis SB2B, S. woodyi ATCC 51908, and S. sediminis HAW-EB3. B: Anoxybacillus flavithermus WK1, Geobacillus kaustophilus HTA426 G. thermodenitrificans NG80-2, Bacillus pumilus SAFR-032, B. subtilis subsp. subtilis str. 168, B. amyloliquefaciens FZB42, B. licheniformis ATCC 14580, B. clausii KSM-K16, B. cereus ATCC 14579, B. anthracis str. Ames, B. halodurans C-125, B. thuringiensis serovar konkukian str. 97–27, and B. weihenstephanensis KBAB4.