Structure and Function of an Unusual Family of Protein Phosphatases

Park, Sang‐Youn; Chao, Xingjuan; Gonzalez-Bonet, Gabriela; Beel, Bryan D.; Bilwes, A.M.; Crane, Brian R.

doi:10.1016/j.molcel.2004.10.018

Cited by 54 publications

(36 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One helical turn away, Asp 143 of CheZ forms an ionic interaction with Lys 109 of CheY. Two other phosphatases, CheC and CheX from Thermotoga maritima, which act on CheY, have different structures (45) featuring extensive ␤-sheets that wrap around exposed ␣-helices. Although the structures of complexes with CheY are not known, a pair of catalytic residues (Glu 13 and Asn 16 in CheC) have been identified by site-directed mutagenesis, and these map to one of a pair of long adjacent helices.…”

Section: Discussionmentioning

confidence: 99%

Structural Characterization of Spo0E-like Protein-aspartic Acid Phosphatases That Regulate Sporulation in Bacilli

Grenha

Rzechorzek

Brannigan

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Spore formation is an extreme response of many bacterial species to starvation. In the case of pathogenic species of Bacillus and Clostridium, it is also a component of disease transmission. Entry into the pathway of sporulation in Bacillus subtilis and its relatives is controlled by an expanded two-component system in which starvation signals lead to the activation of sensor kinases and phosphorylation of the master sporulation response regulator Spo0A. Accumulation of threshold concentrations of Spo0AϳP heralds the commitment to sporulation. Countering the activities of the sensor kinases are phosphatases such as Spo0E, which dephosphorylate Spo0AϳP and inhibit sporulation. Spo0E-like protein-aspartic acid-phosphate phosphatases, consisting of 50 -90 residues, are conserved in sporeforming bacteria and unrelated in sequence to proteins of known structure. Here we determined the structures of the Spo0AϳP phosphatases BA1655 and BA5174 from Bacillus anthracis using nuclear magnetic resonance spectroscopy. Each is composed of two anti-parallel ␣-helices flanked by flexible regions at the termini. The signature SQELD motif (SRDLD in BA1655) is situated in the middle of helix ␣2 with its polar residues projecting outward. BA5174 is a monomer, whereas BA1655 is a dimer. The four-helix bundle structure in the dimer is reminiscent of the phosphotransferase Spo0B and the chemotaxis phosphatase CheZ, although in contrast to these systems, the subunits in BA1655 are in head-to-tail rather than head-tohead apposition. The implications of the structures for interactions between the phosphatases and their substrate Spo0AϳP are discussed.Spore formation is an extreme developmental response of many Gram-positive species of bacteria, exemplified by Bacillus subtilis, to nutrient deprivation (1). It starts with an asymmetric septation, which produces a larger mother cell and a smaller forespore. The mother cell engulfs the forespore and nurtures it during its development into a resistant spore. The spore is released in the final stages upon lysis of the mother cell and can remain dormant in the soil until favorable conditions for growth are restored and it can germinate. Spores are important in the life cycle of a number of human pathogens most notably in the food-borne agents Clostridium botulinum and Bacillus cereus and the anthrax agent Bacillus anthracis (2).Sporulation is energetically expensive, requiring the activation of hundreds of hitherto silent genes at a time when nutrients are scarce. As a result, it is under elaborate control. At the heart of the regulatory system is an expanded two-component signal transduction system, termed the phosphorelay (3). The phosphorelay consists of multiple sensor kinases (4 -6) that, when activated by appropriate environmental, metabolic, and cell cycle stimuli, autophosphorylate on a conserved histidine residue. The phosphoryl group is then relayed via an aspartate on Spo0F and a histidine on Spo0B to an aspartate on Spo0A. Spo0A is a response regulator and the master control elemen...

show abstract

Section: Discussionmentioning

confidence: 99%

Structural Characterization of Spo0E-like Protein-aspartic Acid Phosphatases That Regulate Sporulation in Bacilli

Grenha

Rzechorzek

Brannigan

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Surprisingly, an ␣-helix that mediates FliM self-assembly corresponds to regions of CheC and CheX essential for dephosphorylation of CheY. the same topology with the phosphatases CheC and CheX (24) (Figs. 1 and 2).…”

mentioning

confidence: 88%

“…The middle domain of FliM (FliM M , residues 45-242) has low, but detectable, sequence similarity with the CheC͞CheX͞FliY family of CheY phosphatases (23,24). The CheC and CheX phosphatases have pseudo-2-fold symmetry that likely arose from gene duplication (24).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Structure of FliM provides insight into assembly of the switch complex in the bacterial flagella motor

Park

Lowder

Bilwes

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

142

View full text Add to dashboard Cite

“…The majority of response regulators associated with HKIIIs are single-domain proteins similar to the chemotaxis response regulator CheY (24). In addition, two other types of genes were enriched in the HKIII gene neighborhoods: (i) in 58% of cases, it was a gene coding for CheX phosphatase, which is known to dephosphorylate CheY (25), and (ii) in 60% of cases, it was a gene encoding methyl-accepting chemotaxis protein (MCP) (see Fig. S3 and Data Set S2).…”

Section: Resultsmentioning

confidence: 99%

Class III Histidine Kinases: a Recently Accessorized Kinase Domain in Putative Modulators of Type IV Pilus-Based Motility

et al. 2017

View full text Add to dashboard Cite

Histidine kinases are key components of regulatory systems that enable bacteria to respond to environmental changes. Two major classes of histidine kinases are recognized on the basis of their modular design: classical (HKI) and chemotaxis specific (HKII). Recently, a new type of histidine kinase that appeared to have features of both HKIs and HKIIs was identified and termed HKIII; however, the details of HKIII's relationship to other two classes of histidine kinases, their function, and evolutionary history remain unknown. Here, we carried out genomic, phylogenetic, and protein sequence analyses that allowed us to reveal the unusual evolutionary history of this protein family, formalize its distinctive features, and propose its putative function. HKIIIs are characterized by the presence of sensory domains and the lack of a dimerization domain, which is typically present in all histidine kinases. In addition to a single-domain response regulator, HKIII signal transduction systems utilize CheX phosphatase and, in many instances, an unorthodox soluble chemoreceptor that are usual components of chemotaxis signal transduction systems. However, many HKIII genes are found in genomes completely lacking chemotaxis genes, thus decoupling their function from chemotaxis. By contrast, all HKIIIcontaining genomes also contain pilT, a marker gene for bacterial type IV pilus-based motility, whose regulation is proposed as a putative function for HKIII. These signal transduction systems have a narrow phyletic distribution but are present in many emerging and opportunistic pathogens, thus offering an attractive potential target for future antimicrobial drug design.IMPORTANCE Bacteria adapt to their environment and their hosts by detecting signals and regulating their cellular functions accordingly. Here, we describe a largely unexplored family of signal transduction histidine kinases, called HKIII, that have a unique modular design. While they are currently identified in a relatively short list of bacterial species, this list contains many emerging pathogens. We show that HKIIIs likely control bacterial motility across solid surfaces, which is a key virulence factor in many bacteria, including those causing severe infections. Full understanding of this putative function may help in designing effective drugs against pathogens that will not affect the majority of the beneficial human microbiome.KEYWORDS chemotaxis, evolution, genomics, histidine kinase, motility, pathogens, signal transduction, type IV pili T he transmission of molecular signals in prokaryotes is carried out by the specialized cellular machinery. The simplest signal transduction systems consist of a single protein that is capable of both sensing a signal and directly affecting a cellular

show abstract

Structure and Function of an Unusual Family of Protein Phosphatases

Cited by 54 publications

References 45 publications

Structural Characterization of Spo0E-like Protein-aspartic Acid Phosphatases That Regulate Sporulation in Bacilli

Structural Characterization of Spo0E-like Protein-aspartic Acid Phosphatases That Regulate Sporulation in Bacilli

Structure of FliM provides insight into assembly of the switch complex in the bacterial flagella motor

Class III Histidine Kinases: a Recently Accessorized Kinase Domain in Putative Modulators of Type IV Pilus-Based Motility

Contact Info

Product

Resources

About