Papers of the month

2015

• January 2015
  • Proteases are crucial for the maintenance of protein integrity, but also for controlling the cellular levels of specific proteins. For the LonA protease, it has so far been unknown how the protease can specifically target a selected protein as degradation target. Now, Mukherjee et al. form the lab of Daniel Kearns have studied the degradation of SwrA, a master regulator of flagellar biosynthesis by LonA. They found that the adaptor protein SmiA is required for the productive degradation of SwrA by LonA. This regulatory mechanism is important to prevent hyperflagellation in liquid media.
  • Relevant SubtiWiki pages: LonA, SwrA, SmiA, proteolysis, Daniel Kearns

2014

• December 2014
  • Cell division is facilitated by a molecular machine - the divisome - that assembles at mid-cell in dividing cells. The formation of the cytokinetic Z-ring by FtsZ is regulated by several factors, including the divisome component EzrA. Cleverley et al. now describe the structure of the cytoplasmic domain of EzrA which comprises five linear repeats of an unusual triple helical bundle. The EzrA structure is bent into a semicircle, providing the protein with the potential to interact at both N- and C-termini with adjacent membrane-bound divisome components. The individual repeats, and their linear organization, are homologous to the spectrin proteins that connect actin filaments to the membrane in eukaryotes, and EzrA is proposed to be the founding member of the bacterial spectrin family.
  • Relevant SubtiWiki pages: EzrA, FtsZ, divisome, cell division, Rick Lewis

• November 2014
  • Integration of prophages into coding sequences of the host genome results in loss of function of the interrupted gene. In B. subtilis 168, the SP-beta prophage is inserted into a uncharacterized spore polysaccharide synthesis gene, spsM. In vegetative cells, the lytic cycle is induced in response to DNA damage. In the process, the SP-beta prophage is excised from the genome to form phage particles. Now, Abe et al. demonstrate that the excision of the SP-beta prophage also occurs systematically during sporulation to reconstitute a functional spsM gene from the incomplete yodU and ypqP pseudogenes. Because phage excision is limited to the mother cell genome, and does not occur in the forespore genome, the SP-beta prophage is an integral part of the spore genome. Thus, after germination, the SP-beta prophage is propagated vertically to the progeny. The authors suggest their results indicate that the two pathways of SP-beta prophage excision support both the phage life cycle and normal sporulation of the host cells.
  • Relevant SubtiWiki pages: SP-beta prophage, sporulation, yodU, ypqP, SprA, SprB

• • See also:

• October 2014
  • Drug exporters help the bacterial cell to cope with potentially toxic compounds. The expression of the transporters is usually switched on in response to the transported drugs. Reilman et al. have studied the regulation of the BmrC/BmrD multidrug ABC transporter in B. subtilis. They report that the induction of bmrC-bmrD depends on the translation of a small leader peptide, BmrB. This is the first report on a ribosome-mediated transcriptional attenuation mechanism in the control of a multidrug ABC transporter.
  • Relevant SubtiWiki pages: BmrB, ABC transporter, bmrC-bmrD, AbrB

• September 2014
  • Cyclic di-AMP is the only known essential second messenger. In B. subtilis, it binds the potassium transporter KtrA and the ydaO riboswitch. This riboswitch occurs twice in the genome of B. subtilis: in the untranslated regions of the ydaO gene and the ktrA-ktrB operon. Now, two studies by Ren and Patel and Gao and Serganov report the structure of ydaO riboswitch bound to c-di-AMP. Unexpectedly, the riboswitch structure features two three-way junctions, a turn and a pseudoknot and binds two stapled c-di-AMP molecules.
  • Relevant SubtiWiki pages: riboswitch, YdaO riboswitch, ktrA, metabolism of signalling nucleotides

• August 2014
  • Calcium is important for the activity of many many enzymes, and its cellular homeostasis is therefore important. Now, the previously unknown YetJ protein has been identified as a pH-sensitive calcium leak that allows reducing the inracellular calcium concentration. Chang et al. report the structure of YetJ and explain how two conserved Asp residues sense changes in the pH.
  • Relevant SubtiWiki pages: Metal ion homeostasis (K, Na, Ca, Mg), YetJ

• July 2014
  • T-boxes are regulatory mRNA elements which sense amino acid availability and control the expression of genes encoding aminoacyl-tRNA synthetases and biosynthetic enzymes. Sensing is thought to occur by the interaction of the uncharged tRNA with the T-box thus preventing the formation of a transcription terminator. It has however, not been known whether this regulation involves proteins. Now, Zhang and Ferre-D'Amare show that the B. subtilis glyQ-glyS T-box functions independently of any tRNA-binding protein. They demonstrate that the T-box detects the molecular volume of tRNA 3'-substituents.
  • Relevant SubtiWiki pages: T-box, glyQ

• June 2014
  • Transcription by RNA polymerase is interrupted by pauses that play diverse regulatory roles. However, the determinants of pauses in vivo and their distribution throughout the bacterial genome remain unknown. Using nascent transcript sequencing, Larson et al. identified a 16-nucleotide consensus pause sequence. The pauses result from RNA polymerase-nucleic acid interactions that inhibit next-nucleotide addition. The consensus sequence is enriched at translation start sites in Bacillus subtilis.
  • Relevant SubtiWiki pages: RNA polymerase, transcription, translation

• See a comment on this issue:

• May 2014
  • The knowledge about absolute numbers of molecules of a given protein is often important, e. g. in the context of systems biology or to evaluate the relevance of experimentally observed protein-protein interactions. Muntel et al. from the lab of Dörte Becher have now determined absolute protein concentrations for about 1,000 cytosolic proteins. The results of this study have been added to the SubtiWiki gene pages (see # Expression and regulation). In this study, flagellin was found to be the most abundant protein of B. subtilis.
  • Relevant SubtiWiki pages: Dörte Becher, Michael Hecker, Vincent Fromion, Ulrike Mäder, genome-wide analyses, protein-protein interactions, most abundant proteins

• April 2014
  • DNA repair and recombination involve the unwinding and digestion of the DNA duplex by the AddA-AddB complex from the broken end until they encounter a χ sequence, whereupon the proteins produce a 3′ single-stranded DNA tail onto which they initiate loading of the RecA protein. Now, two studies from the lab of Mark Dillingham address the structure of AddA-AddB complexed to a χ sequence, and the effect of χ binding for processivity and ATP hydrolysis by AddA-AddB.
  • Relevant SubtiWiki pages: Mark Dillingham, DNA repair/ recombination, AddA, AddB

• March 2014
  • In a paper from the labs of Roberto Kolter and Richard Losick PubMed it was reported that B. subtilis synthesizes norspermidine and that this compound is involved in biofilm disassembly. Now, Hobley et al. from the lab of Nicola Stanley-Wall provide compelling evidence that B. subtilis does not produce norspermidine, that previous function annotations of a norspermidine biosynthetic pathway were made in error, and that norspermidine stimulates biofilm formation.
  • Relevant SubtiWiki pages: Nicola Stanley-Wall, biofilm formation, YaaO, GabT

• February 2014
  • Bacteria use quorum sensing to coordinate their behaviour. In B. subtilis, quorum sensing requires the ComX peptide which is sensed by the ComP-ComA two-component system. Now, Oslizlo et al. from the lab of Ines Mandic-Mulec demonstrate that ComQ combines intra- and extracellular sensing, and the authors suggest that this ensures the generation of evolutionarily stable quorum sensing systems.
  • Relevant SubtiWiki pages: Ines Mandic-Mulec, quorum sensing, ComX, ComQ, ComP, ComA

• January 2014
  • The expression of ribosomal proteins is often subject to feedback regulation by the binding of ribosomal proteins to their mRNA leaders. A new study by Fu et al. demonstrate that a heterodimer of RpsF and RpsR binds a structure in the mRNA leader of the rpsF-ssbA-rpsR operon and suggests autoregulation
  • Relevant SubtiWiki pages: ribosomal proteins, RpsF, RpsR

2013

• December 2013
  • Intercellular signaling requires the transfer of information between two different cells. Now, Mastny et al. from the labs of David Rudner and Tim Clausen show how the protease CtpB is activated by substrate binding to cleave off the inhibitory domain of SpoIVFA to allow ultimately allow processing of pro-SigK by SpoIVFB.
  • Relevant SubtiWiki pages: David Rudner, sporulation, CtpB, SpoIVB, SpoIVFA, SpoIVFB

• November 2013
  • Cyclic di-AMP is an essential second messenger in B. subtilis and other Gram-positive bacteria. This molecule has been discovered only in 2008, and a lot of work has recently been devoted to the investigation of its function. This month, Nelson et al. from the lab of Ronald Breaker discovered that c-di-AMP binds to the ydaO riboswitch. This is extremely interesting since the molecule does also bind the KtrA potassium transporter. The ktrA-ktrB operon is also controlled by a ydaO riboswitch. Thus c-di-AMP is the first signalling nucleotide that controls a biological process by binding both a protein and the encoding mRNA.
  • Relevant SubtiWiki pages: Ronald Breaker, ydaO riboswitch, KtrA, ydaO, metabolism of signalling nucleotides

• • Additional papers on c-di-AMP from 2013

• October 2013
  • To initiate DNA replication, the DNA helicase has to bind the oriC region of the chromosome. This binding is assisted by the helicase loader protein. Moreover, the DNA helicase recruits the DNA primase to synthesize RNA primers. Now, Liu et al. determined the structure of the DnaC-DnaI-DnaG complex and present novel insights into insights the mechanism of bacterial primosome assembly.
  • Relevant SubtiWiki pages: DnaC, DnaI, DnaG, SubtInteract, replisome, DNA replication

• September 2013
  • Biofilms of B. subtilis consist of cells in a matrix made up of extracellular polysaccharides, the amyloid-like TasA protein, and the hydrophobic protein BslA. Now, Hobley et al. from the lab of Nicola Stanley-Wall determined the structure of BslA and found that the protein has an extremely hydrophobic cap domain that acts like a raincoat for the biofilm. The authors suggest that BslA is a bacterial hydrophobin.
  • Relevant SubtiWiki pages: Nicola Stanley-Wall, biofilm formation, BslA

• • A comment on this paper:

• August 2013
  • In cells, the concentration of ribonucleotides by far exceeds that of deoxyribonucleotides. This poses problems since the DNA polymerase incorporates one rNTP every 2.3 kb during chromosome replication. Now, Yao et al. investigated how these misincorporations are repaired. They demonstrate that this repair is initiated by RNase HII that nicks DNA at single rNMP residues to initiate replacement with dNMPs.
  • Relevant SubtiWiki pages: DNA replication, DNA repair, rnhB, rnhC, mutS, mutL

• July 2013
  • Ca²⁺ efflux by Ca²⁺ cation antiporter (CaCA) proteins is important for maintenance of Ca²⁺ homeostasis across the cell membrane. Now, Wu et al. determined the structure of the B. subtilis Ca²⁺/H⁺ antiporter protein ChaA. By structural and mutational analyses, they establish structural bases for mechanisms of Ca²⁺/H⁺ exchange and its pH regulation. Moreover, this work also sheds light on the evolutionary adaptation to different energy modes in the CaCA protein family.
  • Relevant SubtiWiki pages: ChaA, membrane proteins, metal ion homeostasis (K, Na, Ca, Mg)

• June 2013
  • DNA transfer across membranes is important in many fundamental processes. However, the molecular mechanisms behind this transport are only poorly understood. Now, Fiche et al. analysed the assembly and molecular architecture of the SpoIIIE DNA translocation complex. This study reveals that in contrast to a previous model, DNA transfer occurs through an aqueous DNA-conducting pore that could be structurally maintained by the divisional machinery, with SpoIIIE acting as a checkpoint preventing membrane fusion until completion of chromosome segregation.
  • Relevant SubtiWiki pages: sporulation, SpoIIIE, DNA condensation/ segregation

• May 2013
  • Paul et al. demonstrate that the orientation of the genes on the chromosome has a significant impact on their evolution: Gene encoded on the lagging strand evolve faster than those on the leading strand. This faster evolution is caused by collisions between the DNA replication and transcription machineries that result in DNA damage and subsequent fixation of errors as mutations. Importantly, essential genes are strongly underrepresented on the lagging strand thus providing a "built-in" protection of the encoded important proteins against possible deleterious mutations.
  • Relevant SubtiWiki pages: transcription, DNA replication, essential genes

• April 2013
  • Usually, cell wall synthesis is regarded as being essential for B. subtilis. Now, Mercier et al. from the lab of Jeff Errington show that excess biosynthesis of membranes is sufficient to drive the formation of cell wall-less L-forms in B. subtilis. Interestingly, this cell form is even independent of the essential cell division protein FtsZ.
  • Relevant SubtiWiki pages: Jeff Errington, biosynthesis of lipids, cell wall synthesis, cell division, FtsZ

• March 2013
  • The mechanism of membrane fission in bacteria has been a long-standing enigma. Now, Doan et al. from the lab of David Rudner demonstrate how the FisB protein (previously YunB) mediates membrane fission during sporulation This activity of FisB is based on its ability to bind to lipids, specifically to cardiolipin.
  • Relevant SubtiWiki pages: David Rudner, FisB, sporulation

• See also:

• February 2013
  • For many essential genes of B. subtilis, it is not clear why they are essential in B. subtilis but not in closely related species. Strikingly, this is the case for RNases such as RNases III and Y. Now, Durand et al. from the lab of Ciaran Condon have identified the reason for the essentiality of RNase III: This enzyme is required to degrade phage encoded toxin mRNA molecules thus protecting the cell from lysis caused by the encoded toxins. Indeed, RNase III is dispensable in a strain lacking the Skin element and the SPß prophage that harbor the corresponding toxin genes.
  • Relevant SubtiWiki pages: Ciaran Condon, RNase III, essential genes, yonT, txpA, toxins, antitoxins and immunity against toxins

• A comment on this paper:

• See also:

• January 2013
  • Castaing et al. from the lab of Kumaran Ramamurthi show how ATP hydrolysis drives the self-association of SpoIVA into nucleotide-free filaments which then serve as a platform for the assembly of the spore coat starting with SpoVM. Together with the december's paper of the month these works demonstrate how ATP hydrolysis may contribute to different processes within a protein such as global conformational changes and self-assembly.
  • Relevant SubtiWiki pages: Kumaran Ramamurthi, SpoIVA, sporulation

2012

• December 2012
  • Kim et al. show how the ATP hydrolysis controls the global conformation of the SecA translocase and drives protein secretion. The intricate network of structural interactions, which couple local electrostatic changes during ATP hydrolysis to global conformational and dynamic changes in SecA, form the foundation of the allosteric mechanochemistry that efficiently harnesses the chemical energy stored in ATP to drive complex mechanical processes.
  • Relevant SubtiWiki pages: SecA, protein secretion

• November 2012
  • Watson and Fedor identify the first ATP-responsive riboswitch. This riboswitch controls the expression of the ydaO gene and the ktrA-ktrB operon. Gene expression is decreased upon binding of ATP to the riboswitch. In consequence, the target genes are induced if the energy charge of the cell is low.
  • Relevant SubtiWiki pages: ydaO, ydaO riboswitch, riboswitch, ktrA-ktrB

• October 2012
  • Plata et al. from the labs of Dennis Vitkup and Uwe Sauer use a probabilistic approach to annotate genome-scale metabolic networks that integrates sequence homology and context-based correlations to functionally annotate so far unknown enzymes.
  • Relevant SubtiWiki pages: ykgB, spsI, spsJ, Uwe Sauer, Dennis Vitkup, metabolism

• September 2012
  • Chiba and Ito studied how the translation of YidC2, a membrane protein biogenesis factor, is controlled by SpoIIIJ availability via ribosome stalling of the mifM mRNA.
  • Relevant SubtiWiki pages: Koreaki Ito, translation, YidC2, SpoIIIJ, mifM

• August 2012
  • Houry et al. from the lab of Romain Briandet showed how motile Bacillus thuringiensis bacteria can penetrate a Staphylococcus aureus biofilm and eventually kill the biofilm bacteria with their antibacterial compounds.
  • Relevant SubtiWiki pages: Romain Briandet, Stephane Aymerich, biofilm formation, biosynthesis of antibacterial compounds

• July 2012
  • Dago et al. from the lab of Hendrik Szurmant studied the interactions between histidine kinase domains of two-component systems that result in autophosphorylation.
  • Relevant SubtiWiki pages: Hendrik Szurmant, Jim Hoch, two-component systems, KinA, KinD, protein-protein interactions

• June 2012
  • Kolodkin-Gal et al. from the labs of Roberto Kolter and Richard Losick report that D-amino acids and norspermidine act together in preventing biofilm formation and triggering biofilm disassembly. However, this was shown to be wrong in February 2014 (see Paper of the month, Feb. 2014)

• May 2012
  • Elsholz et al. from the lab of Ulf Gerth demonstrate that protein phosphorylation on arginine residues is of great importance for B. subtilis. In addition to the previously identified target CtsR, 86 proteins are shown to be phosphorylated on arginine. The protein arginine kinase and phosphatase, McsB and YwlE, respectively, may thus have an important regulatory role in B. subtilis.
  • Relevant SubtiWiki pages: Ulf Gerth, Kürsad Turgay, Ulrike Mäder, Dörte Becher, Michael Hecker, phosphoproteins, protein kinases and phosphatases, McsB, YwlE

• April 2012
  • Meisner et al. and Levdikov et al. from the labs of Charles Moran and Tony Wilkinson, respectively, have reported the structure of the complex between SpoIIQ and SpoIIIAH. These two proteins interact through two membranes to connect the forespore and the mother cell during sporulation. The structure of the complex suggests that it is the extracellular component of a gap junction-like intercellular channel for the traffic of proteins between the two compartments.
  • Relevant SubtiWiki pages: Charles Moran, Tony Wilkinson, sporulation, SpoIIQ, SpoIIIAH

• March 2012
  • Buescher et al. and Nicolas et al. from the BaSysBio consortium diected by Philippe Noirot studied the dynamic metabolic and transcriptional responses of B. subtilis to changes of the growth conditions. One of the major issues is the adaptation of the cells upon a nutrient switch from glucose to malate and vice versa. Importantly, the study by Nicholas et al. provides an analysis of gene expression at 104 different conditions as revealed by tiling arrays.
  • Relevant SubtiWiki pages: Philippe Noirot, Michael Hecker, Uwe Völker, Philippe Bessières, Uwe Sauer, Stephane Aymerich, Tony Wilkinson, metabolism, transcription, CcpA, Sigma factors, sRNAs, Rho

• A comment on these papers:

• February 2012
  • Levine et al. from the lab of Michael Elowitz show how B. subtilis cells can defer sporulation for multiple cell cycles in response to sudden environmental stress. This deferral is controlled by a pulsed positive feedback loop in which phosphorelay kinase expression is activated by pulses of Spo0A phosphorylation.
  • Relevant SubtiWiki pages: Michael Elowitz, Jonathan Dworkin, phosphorelay, sporulation, Spo0A

• A comment on this paper:

• January 2012
  • Segev et al. from the lab of Sigal Ben-Yehuda demonstrate that ribosomal RNAs are degraded in aging spores by RNase Y. Moreover, the authors show that individual mRNAs experience degradation or accumulation in spores. The study suggests that the kinetics of spore germination depends on the conditions that a spore had experienced before.
  • Relevant SubtiWiki pages: Sigal Ben-Yehuda, RNase Y, germination, RNases

2011

• December 2011
  • Bange et al. from the lab of Irmgard Sinning show how the FlhG protein activates the SRP-GTPase FlhF. The study sheds light on the evolutionary transition from RNA- to protein-driven activation in SRP-GTPases.
  • Relevant SubtiWiki pages: Irmgard Sinning, FlhF, FlhG, signal recognition particle, motility and chemotaxis

• November 2011
  • Locke et al. show how the SigB-dependent general stress response is controlled by signals using stochastic pulse frequency modulation through a compact regulatory architecture.
  • Relevant SubtiWiki pages: Michael Elowitz, SigB, General stress response

• October 2011
  • Richards et al. identify the nudix hydrolase RppH as the pyrophosphohydrolase that triggers 5'-exonucleolytic degradation of mRNA by RNase J1 in B. subtilis.
  • Relevant SubtiWiki pages: David Bechhofer, Ciaran Condon, RNA processing and degradation, nudix hydrolase, RppH, RNase J1

• September 2011
  • A series of papers deals with RNA processing and degradation in B. subtilis. Three papers establish that RNase Y is the functional equivalent of RNase E from E. coli. Moreover, the role of RNase J1 in endonucleolytic cleavage of the trp leader mRNA is demonstrated.
  • Relevant SubtiWiki pages: David Bechhofer, Rick Lewis, Ulrike Mäder, Harald Putzer, Jörg Stülke, RNases, RNA degradosome, RNase Y, RNase Y targets, RNase J1

• August 2011
  • Chi et al. demonstrate that S-bacillithiolation of the repressor OhrR and of four enzymes of the methionine biosynthesis pathway protects the B. subtilis cell against hypochlorite stress.
  • Relevant SubtiWiki pages: Haike Antelmann, Dörte Becher, Ulrike Mäder, resistance against oxidative and electrophile stress, Spx regulon, CtsR regulon, PerR regulon, OhrR, MetE, YxjG, PpaC, SerA, YphP

• July 2011
  • Domínguez-Escobar et al. from Rut Carballido-Lopez' lab and Garner et al. report that movement of actin-like filaments is driven by the peptidoglycan elongation machinery. Both papers suggest that the MreB-like filaments serve to restrict the mobility of the peptidoglycan synthesizing machinery
    
  • Relevant SubtiWiki pages: Rut Carballido-Lopez, David Rudner, MreB, MreBH, Mbl, MreC, MreD, PbpA, RodA, RodZ, penicillin-binding proteins, cell shape, cell wall synthesis, cell wall biosynthetic complex

• A comment on these papers:

• June 2011
  • Oppenheimer-Shaanan et al. from Sigal Ben-Yehuda's lab report that cyclic di-AMP acts as a secondary messenger that couples DNA integrity with progression of sporulation
    
  • Relevant SubtiWiki pages: Sigal Ben-Yehuda, DisA, GdpP, metabolism of signalling nucleotides, cell division

• May 2011
  • Miles et al. identified the enzyme for the key final step in the biosynthesis of queuosine, a hypermodified base found in the wobble positions of tRNA Asp, Asn, His, and Tyr from bacteria to man
    
  • Relevant SubtiWiki pages: QueG, translation