Response regulators of bacterial signal transduction systems: Selective domain shuffling during evolution

Abstract

Response regulators of bacterial sensory transduction systems generally consist of receiver module domains covalently linked to effector domains. The effector domains include DNA binding and/or catalytic units that are regulated by sensor kinase-catalyzed aspartyl phosphorylation within their receiver modules. Most receiver modules are associated with three distinct families of DNA binding domains, but some are associated with other types of DNA binding domains, with methylated chemotaxis protein (MCP) demethylases, or with sensor kinases. A few exist as independent entities which regulate their target systems by noncovalent interactions. In this study the molecular phylogenies of the receiver modules and effector domains of 49 fully sequenced response regulators and their homologues were determined. The three major, evolutionarily distinct, DNA binding domains found in response regulators were evaluated for their phylogenetic relatedness, and the phylogenetic trees obtained for these domains were compared with those for the receiver modules. Members of one family (family 1) of DNA binding domains are linked to large ATPase domains which usually function cooperatively in the activation of E. coli sigma 54-dependent promoters or their equivalents in other bacteria. Members of a second family (family 2) always function in conjunction with the E. coli sigma 70 or its equivalent in other bacteria. A third family of DNA binding domains (family 3) functions by an uncharacterized mechanism involving more than one sigma factor. These three domain families utilize distinct helix-turn-helix motifs for DNA binding. The phylogenetic tree of the receiver modules revealed three major and several minor clusters of these domains. The three major receiver module clusters (clusters 1, 2, and 3) generally function with the three major families of DNA binding domains (families 1, 2, and 3, respectively) to comprise three classes of response regulators (classes 1, 2, and 3), although several exceptions exist. The minor clusters of receiver modules were usually, but not always, associated with other types of effector domains. Finally, several receiver modules did not fit into a cluster. It was concluded that receiver modules usually diverged from common ancestral protein domains together with the corresponding effector domains, although domain shuffling, due to intragenic splicing and fusion, must have occurred during the evolution of some of these proteins. Multiple sequence alignments of the 49 receiver modules and their various types of effector domains, together with other homologous domains, allowed definition of regions of striking sequence similarity and degrees of conservation of specific residues. Sequence data were correlated with structure/function when such information was available.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular characterization of the 1,3-propanediol (1,3-PD) operon of Clostridium butyricum

“…dhaS and dhaA encode proteins of 405 and 351 amino acid residues (molecular masses of 46,440 and 40,438 Da), respectively, with significant homology to a number of sensor histidine kinases and response regulators, respectively, which compose the archetypal prokaryotic two-component signal transduction system (38,39).…”

Crystal Structure of Circadian Clock Protein KaiA from Synechococcus elongatus

“…The NH 2 -terminal portion (residues 1-135) of this domain is structurally similar to the response regulator receiver family, which is involved in a wide range of regulatory processes (29), discussed in detail below. This domain consists of a central five-stranded (␤1 to ␤5) parallel ␤-sheet flanked by two groups of ␣-helices (␣1, ␣4 and ␣2, ␣3) packed on either side of the ␤-sheet and an additional ␣-helix (␣5) lying near the amino terminus of the central ␤-strand (Fig.…”

The Streptomyces coelicolor A3(2) lipAR operon encodes an extracellular lipase and a new type of transcriptional regulator The GenBank accession numbers for the sequences described in this paper are AF009336 and U03114.

“…lez et al , 1997). These proteins have a type 3 DNA-binding domain, as defined by Pao & Saier (1995), and range in size between 200 and 250 amino acids ; most of them are response regulators of the UhpA family, but others (the LuxR subfamily ; Fuqua et al, 1994) are cell-densityresponding regulators that use homoserine lactones as effectors. In addition, there are some that cannot be grouped with members of either subfamily.…”

“…For example, GerE of Bacillus subtilis consists exclusively of the DNA-binding domain, and MalT, which is much larger, is a transcriptional activator of the maltose utilization regulon of E. coli (Schleif, 1996). Until the recent description of a MalT homologue, AcoK of K. pneumoniae (Peng et al, 1997), MalT did not appear to resemble any other regulatory proteins outside its DNAbinding domain, and in fact was considered unusually large for a regulator (Pao & Saier, 1995 ;Schleif, 1996). The LipR protein of S. exfoliatus M11 has a homologous DNA-binding domain and is similar in size to MalT ; in fact, limited similarity was observed between both Cloning of S. coelicolor A3(2) lipase and regulator proteins and AcoK (Servı!…”