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I am a biochemist based in Tartu, Estonia, working on translation and stringent response in bacteria. For more info visit my lab webpage http://www.tuit.ut.ee/hauryliuk/hauryliuklab/Welcome.html

stringent response
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March 13, 2012
10:20 AM
913 views

ppGpp induces production of fruiting bodies in Myxococcus xanthus

by Vasili Hauryliuk in stringent response

E. coli is boring, admit it. At least in comparison with Myxococcus xanthus: a self-organized, predatory saprotrophic single-species biofilm called a swarm according to Wikipedia. Now that sounds exciting! I wish one day somebody would call me "a self-organized, predatory biofilm called a swarm"! That would make a lovely email signature: "Vasili Hauryliuk, PhD, self-organized, predatory biofilm called a swarm". Hell yes.But I digress. Stringent response (or, to be more specific, ........ Read more »

Harris BZ, Kaiser D, & Singer M. (1998) The guanosine nucleotide (p)ppGpp initiates development and A-factor production in myxococcus xanthus. Genes , 12(7), 1022-35. PMID: 9531539

Konovalova A, Löbach S, & Søgaard-Andersen L. (2012) A RelA-dependent two-tiered regulated proteolysis cascade controls synthesis of a contact-dependent intercellular signal in Myxococcus xanthus. Molecular microbiology. PMID: 22404381

March 12, 2012
07:44 AM
483 views

Measuring nucleotide concentrations inside the living cells

by Vasili Hauryliuk in stringent response

Taking biological system apart and doing experiments in vitro is a very powerful approach. However, Nature has loads of dirty tricks up her sleeve, so doing experiments in vivo is more kosher - at least you get all the concentrations rights and will have all of the components present in the system.Cells use a whole plethora of nucleotide-based messengers (Pesavento and Hengge, Curr. Opin. Microbiol. 2009), and following concentrations of these in vivo is something microbiologists would love........ Read more »

Paige JS, Nguyen-Duc T, Song W, & Jaffrey SR. (2012) Fluorescence imaging of cellular metabolites with RNA. Science (New York, N.Y.), 335(6073), 1194. PMID: 22403384

Paige JS, Wu KY, & Jaffrey SR. (2011) RNA mimics of green fluorescent protein. Science (New York, N.Y.), 333(6042), 642-6. PMID: 21798953

Christen M, Kulasekara HD, Christen B, Kulasekara BR, Hoffman LR, & Miller SI. (2010) Asymmetrical distribution of the second messenger c-di-GMP upon bacterial cell division. Science (New York, N.Y.), 328(5983), 1295-7. PMID: 20522779

Benach J, Swaminathan SS, Tamayo R, Handelman SK, Folta-Stogniew E, Ramos JE, Forouhar F, Neely H, Seetharaman J, Camilli A.... (2007) The structural basis of cyclic diguanylate signal transduction by PilZ domains. The EMBO journal, 26(24), 5153-66. PMID: 18034161

August 4, 2011
06:42 AM
1,306 views

Observing protein synthesis inside the living mammalian cell

by Vasili Hauryliuk in stringent response

Biologists really love seeing things for themselves. Take for instance the central dogma: DNA - RNA - protein. It all well and good when represented and childish-looking blobs fulling around and passing amino acids one to each other, but how about it actually happening in the real 3D cell stuffed with other goodies? Well, obviously, people tried looking into the question.First option is you can to label fluorescently components of the machinery - ribosomes, mRNAs, factors - and plonk t........ Read more »

Blanchard SC. (2009) Single-molecule observations of ribosome function. Current opinion in structural biology, 19(1), 103-9. PMID: 19223173

Barhoom S, Kaur J, Cooperman BS, Smorodinsky NI, Smilansky Z, Ehrlich M, & Elroy-Stein O. (2011) Quantitative single cell monitoring of protein synthesis at subcellular resolution using fluorescently labeled tRNA. Nucleic acids research. PMID: 21795382

Uemura S, Aitken CE, Korlach J, Flusberg BA, Turner SW, & Puglisi JD. (2010) Real-time tRNA transit on single translating ribosomes at codon resolution. Nature, 464(7291), 1012-7. PMID: 20393556

July 6, 2011
05:18 AM
1,237 views

Single-molecule investigations of the stringent response machinery in living bacterial cells

by Vasili Hauryliuk in stringent response

Wikipedia: "reductionism, an approach to understanding the nature of complex things by reducing them to the interactions of their parts, or to simpler or more fundamental things". This approach was very successful in unrevealing the basic mechanisms of biological systems. Modern biochemistry is reductionism in its pure form: we purify individual components, mix them together in a test tube and make this in vitro system jump through the hoops and ........ Read more »

Xie XS, Choi PJ, Li GW, Lee NK, & Lia G. (2008) Single-molecule approach to molecular biology in living bacterial cells. Annual review of biophysics, 417-44. PMID: 18573089

Potrykus K, & Cashel M. (2008) (p)ppGpp: still magical?. Annual review of microbiology, 35-51. PMID: 18454629

Gallant J, Palmer L, & Pao CC. (1977) Anomalous synthesis of ppGpp in growing cells. Cell, 11(1), 181-5. PMID: 326415

Brian P. English, Vasili Hauryliuk, Arash Sanamrad, Stoyan Tankov, Nynke H. Dekker, and Johan Elf. (2011) Single-molecule investigations of the stringent response machinery in living bacterial cells. Proceedings of the National Academy of Sciences of the United States of America. info:/

May 27, 2011
06:42 AM
1,267 views

Systems biology approach to stringent response

by Vasili Hauryliuk in stringent response

Bacterial cells constantly need to monitor their environment and act accordingly.The trouble is, bacteria are very small and when you are so very small, all the effects of being quantized in terms of molecule numbers are becoming very strong: number of mRNA molecules for a certain gene is an integer value, and not a very high at that, events of receptor getting activated or RNA polymerase binding to the promoter are stochastic in nature, and since not too many of the individu........ Read more »

Potrykus K, & Cashel M. (2008) (p)ppGpp: still magical?. Annual review of microbiology, 35-51. PMID: 18454629

Mittenhuber G. (2001) Comparative genomics and evolution of genes encoding bacterial (p)ppGpp synthetases/hydrolases (the Rel, RelA and SpoT proteins). Journal of molecular microbiology and biotechnology, 3(4), 585-600. PMID: 11545276

Dahl JL, Kraus CN, Boshoff HI, Doan B, Foley K, Avarbock D, Kaplan G, Mizrahi V, Rubin H, & Barry CE 3rd. (2003) The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Proceedings of the National Academy of Sciences of the United States of America, 100(17), 10026-31. PMID: 12897239

Sureka K, Ghosh B, Dasgupta A, Basu J, Kundu M, & Bose I. (2008) Positive feedback and noise activate the stringent response regulator rel in mycobacteria. PloS one, 3(3). PMID: 18335046

Ghosh S, Sureka K, Ghosh B, Bose I, Basu J, & Kundu M. (2011) Phenotypic heterogeneity in mycobacterial stringent response. BMC systems biology, 18. PMID: 21272295

Elowitz MB, Levine AJ, Siggia ED, & Swain PS. (2002) Stochastic gene expression in a single cell. Science (New York, N.Y.), 297(5584), 1183-6. PMID: 12183631

Larson DR, Singer RH, & Zenklusen D. (2009) A single molecule view of gene expression. Trends in cell biology, 19(11), 630-7. PMID: 19819144

Alon U. (2007) Network motifs: theory and experimental approaches. Nature reviews. Genetics, 8(6), 450-61. PMID: 17510665

Ingolia NT, & Murray AW. (2007) Positive-feedback loops as a flexible biological module. Current biology : CB, 17(8), 668-77. PMID: 17398098

Lidstrom ME, & Konopka MC. (2010) The role of physiological heterogeneity in microbial population behavior. Nature chemical biology, 6(10), 705-12. PMID: 20852608

Taniguchi Y, Choi PJ, Li GW, Chen H, Babu M, Hearn J, Emili A, & Xie XS. (2010) Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells. Science (New York, N.Y.), 329(5991), 533-8. PMID: 20671182

Balaban NQ, Merrin J, Chait R, Kowalik L, & Leibler S. (2004) Bacterial persistence as a phenotypic switch. Science (New York, N.Y.), 305(5690), 1622-5. PMID: 15308767

May 9, 2011
03:44 PM
822 views

Antibiotics affecting ribosome's protein composition

by Vasili Hauryliuk in stringent response

Antibiotics kill bugs; and about a half of them are doing so by messing up translation. That usually means that the ribosome is stalled at a certain step, be it initiation or elongation or ribosomal recycling.But it is not always just that. Sometimes antibiotics also mess up the ribosome itself and affect its composition.Exhibit A: kasugamycin, an antibiotic that inhibits translation initiation in bacteria by interfering with binding of the the initiator ........ Read more »

Wilson DN. (2009) The A-Z of bacterial translation inhibitors. Critical reviews in biochemistry and molecular biology, 44(6), 393-433. PMID: 19929179

Schluenzen F, Takemoto C, Wilson DN, Kaminishi T, Harms JM, Hanawa-Suetsugu K, Szaflarski W, Kawazoe M, Shirouzu M, Nierhaus KH.... (2006) The antibiotic kasugamycin mimics mRNA nucleotides to destabilize tRNA binding and inhibit canonical translation initiation. Nature structural , 13(10), 871-8. PMID: 16998488

Schuwirth BS, Day JM, Hau CW, Janssen GR, Dahlberg AE, Cate JH, & Vila-Sanjurjo A. (2006) Structural analysis of kasugamycin inhibition of translation. Nature structural , 13(10), 879-86. PMID: 16998486

Kaberdina AC, Szaflarski W, Nierhaus KH, & Moll I. (2009) An unexpected type of ribosomes induced by kasugamycin: a look into ancestral times of protein synthesis?. Molecular cell, 33(2), 227-36. PMID: 19187763

Siibak T, Peil L, Dönhöfer A, Tats A, Remm M, Wilson DN, Tenson T, & Remme J. (2011) Antibiotic-induced ribosomal assembly defects result from changes in the synthesis of ribosomal proteins. Molecular microbiology, 80(1), 54-67. PMID: 21320180

Nevo-Dinur K, Nussbaum-Shochat A, Ben-Yehuda S, & Amster-Choder O. (2011) Translation-independent localization of mRNA in E. coli. Science (New York, N.Y.), 331(6020), 1081-4. PMID: 21350180

Tzareva NV, Makhno VI, & Boni IV. (1994) Ribosome-messenger recognition in the absence of the Shine-Dalgarno interactions. FEBS letters, 337(2), 189-94. PMID: 8287975

Andreev DE, Terenin IM, Dunaevsky YE, Dmitriev SE, & Shatsky IN. (2006) A leaderless mRNA can bind to mammalian 80S ribosomes and direct polypeptide synthesis in the absence of translation initiation factors. Molecular and cellular biology, 26(8), 3164-9. PMID: 16581790

Montero Llopis P, Jackson AF, Sliusarenko O, Surovtsev I, Heinritz J, Emonet T, & Jacobs-Wagner C. (2010) Spatial organization of the flow of genetic information in bacteria. Nature, 466(7302), 77-81. PMID: 20562858

May 8, 2011
09:07 AM
601 views

Yes we can't!

by Vasili Hauryliuk in stringent response

In a recent paper by Shachrai at al. (which I discussed in detail here) a SpoT knock-out E. coli strain was reported, even though it is known that this strain is lethal. The good news is that now it is all cleared up.The authors of the original paper wrote an erratum saying that yes, their SpoT knock-out was not just a SpoT knock-out; it has compensatory mutations. More specifically, RelA (which makes the brunt of the ppGpp in the cell) was compromised by mutations involved i........ Read more »

Shachrai, I., Zaslaver, A., Alon, U., & Dekel, E. (2010) Cost of Unneeded Proteins in E. coli Is Reduced after Several Generations in Exponential Growth. Molecular Cell, 38(5), 758-767. DOI: 10.1016/j.molcel.2010.04.015

Xiao H, Kalman M, Ikehara K, Zemel S, Glaser G, & Cashel M. (1991) Residual guanosine 3',5'-bispyrophosphate synthetic activity of relA null mutants can be eliminated by spoT null mutations. The Journal of biological chemistry, 266(9), 5980-90. PMID: 2005134

Datsenko KA, & Wanner BL. (2000) One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proceedings of the National Academy of Sciences of the United States of America, 97(12), 6640-5. PMID: 10829079

Gropp M, Strausz Y, Gross M, & Glaser G. (2001) Regulation of Escherichia coli RelA requires oligomerization of the C-terminal domain. Journal of bacteriology, 183(2), 570-9. PMID: 11133950

Gentry DR, & Burgess RR. (1989) rpoZ, encoding the omega subunit of Escherichia coli RNA polymerase, is in the same operon as spoT. Journal of bacteriology, 171(3), 1271-7. PMID: 2646273

March 30, 2011
08:26 AM
1,016 views

Doing kinetics in vivo and in vitro - what can go wrong?

by Vasili Hauryliuk in stringent response

When you study an enzyme-catalyzed reaction happening in the cell, there are basically 3 things you want to know:1) how fast?2) how sensitive to the substrate concentration?3) how specific?In terms of the Michaelis-Menten kinetics that would be kcat, KM and kcat/KM. These all can be measured in vitro, given that you can purify your protein of interest and set up an assay to follow the reaction. But that's in vitro, you say, and how about in vivo? May be everything is different there? What a plea........ Read more »

Hurley JM, Cruz JW, Ouyang M, & Woychik NA. (2011) Bacterial toxin RelE mediates frequent codon-independent mRNA cleavage from the 5' end of coding regions in vivo. The Journal of biological chemistry. PMID: 21324908

Neubauer C, Gao YG, Andersen KR, Dunham CM, Kelley AC, Hentschel J, Gerdes K, Ramakrishnan V, & Brodersen DE. (2009) The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE. Cell, 139(6), 1084-95. PMID: 20005802

Pedersen K, Zavialov AV, Pavlov MY, Elf J, Gerdes K, & Ehrenberg M. (2003) The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site. Cell, 112(1), 131-40. PMID: 12526800

Burmann BM, Schweimer K, Luo X, Wahl MC, Stitt BL, Gottesman ME, & Rösch P. (2010) A NusE:NusG complex links transcription and translation. Science (New York, N.Y.), 328(5977), 501-4. PMID: 20413501

February 16, 2011
01:14 PM
1,174 views

Abort! Abort!

by Vasili Hauryliuk in stringent response

Sometimes things go so wrong that it is just easier to start all over again. Bacteria have these situations too - it's not just us, humans! - and the central dogma of molecular biology (DNA replication, transcription and translation) is no exception.In essence all the three steps of the central dogma share the very same basic topology: there is a message that gets read, there is a tool that reads it and there is a product. It looks like so:Say, in the case of translation mRNA (the mess........ Read more »

Borukhov S, Sagitov V, & Goldfarb A. (1993) Transcript cleavage factors from E. coli. Cell, 72(3), 459-66. PMID: 8431948

Toulmé F, Mosrin-Huaman C, Sparkowski J, Das A, Leng M, & Rahmouni AR. (2000) GreA and GreB proteins revive backtracked RNA polymerase in vivo by promoting transcript trimming. The EMBO journal, 19(24), 6853-9. PMID: 11118220

Pedersen K, Zavialov AV, Pavlov MY, Elf J, Gerdes K, & Ehrenberg M. (2003) The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site. Cell, 112(1), 131-40. PMID: 12526800

Orlova M, Newlands J, Das A, Goldfarb A, & Borukhov S. (1995) Intrinsic transcript cleavage activity of RNA polymerase. Proceedings of the National Academy of Sciences of the United States of America, 92(10), 4596-600. PMID: 7538676

Kassavetis GA, & Geiduschek EP. (1993) RNA polymerase marching backward. Science (New York, N.Y.), 259(5097), 944-5. PMID: 7679800

Richter R, Rorbach J, Pajak A, Smith PM, Wessels HJ, Huynen MA, Smeitink JA, Lightowlers RN, & Chrzanowska-Lightowlers ZM. (2010) A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. The EMBO journal, 29(6), 1116-25. PMID: 20186120

Shoemaker CJ, Eyler DE, & Green R. (2010) Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop-off to initiate no-go decay. Science (New York, N.Y.), 330(6002), 369-72. PMID: 20947765

Atkinson GC, Baldauf SL, & Hauryliuk V. (2008) Evolution of nonstop, no-go and nonsense-mediated mRNA decay and their termination factor-derived components. BMC evolutionary biology, 290. PMID: 18947425

Antonicka H, Ostergaard E, Sasarman F, Weraarpachai W, Wibrand F, Pedersen AM, Rodenburg RJ, van der Knaap MS, Smeitink JA, Chrzanowska-Lightowlers ZM.... (2010) Mutations in C12orf65 in patients with encephalomyopathy and a mitochondrial translation defect. American journal of human genetics, 87(1), 115-22. PMID: 20598281

Zaher HS, & Green R. (2009) Quality control by the ribosome following peptide bond formation. Nature, 457(7226), 161-6. PMID: 19092806

February 11, 2011
11:39 AM
1,388 views

Regulation of mitochondrial protein transport

by Vasili Hauryliuk in stringent response

Mitochondria have their own genome, own translational machinery, own ribosomes, but still, most of the proteins they import from the cytosole. And this they do using two protein complexes in the outer and inner membranes: TOM (Transporter Outer Membrane) and TIM (Transporter Inner Membrane). TOM itself consists of several subunits: Tom40 forms a pore through which proteins get transported, Tom20 and Tom70 work as receptors recognizing the mitochondrial proteins in the cytoplasm, and several........ Read more »

Chacinska A, Koehler CM, Milenkovic D, Lithgow T, & Pfanner N. (2009) Importing mitochondrial proteins: machineries and mechanisms. Cell, 138(4), 628-44. PMID: 19703392

Schmidt O, Harbauer AB, Rao S, Eyrich B, Zahedi RP, Stojanovski D, Schönfisch B, Guiard B, Sickmann A, Pfanner N.... (2011) Regulation of mitochondrial protein import by cytosolic kinases. Cell, 144(2), 227-39. PMID: 21215441

February 8, 2011
03:30 PM
923 views

Observer effect in biology: Schrödinger's cat mitochondria

by Vasili Hauryliuk in stringent response

All quantum physicists know that observation itself changes the object of observation. We will never know what things are actually doing when we are not looking, just because if in order to figure out what they do, we need to look; it's catch-22. But that's quantum physics, you say. How about molecular biology?Well, here is an example. Mitochondria, as you know, have their own genome, and they translate it, and they do so in a very funky way. Ever translation termination........ Read more »

Neubauer C, Gao YG, Andersen KR, Dunham CM, Kelley AC, Hentschel J, Gerdes K, Ramakrishnan V, & Brodersen DE. (2009) The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE. Cell, 139(6), 1084-95. PMID: 20005802

Andreev D, Hauryliuk V, Terenin I, Dmitriev S, Ehrenberg M, & Shatsky I. (2008) The bacterial toxin RelE induces specific mRNA cleavage in the A site of the eukaryote ribosome. RNA (New York, N.Y.), 14(2), 233-9. PMID: 18083838

Pedersen K, Zavialov AV, Pavlov MY, Elf J, Gerdes K, & Ehrenberg M. (2003) The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site. Cell, 112(1), 131-40. PMID: 12526800

Young DJ, Edgar CD, Murphy J, Fredebohm J, Poole ES, & Tate WP. (2010) Bioinformatic, structural, and functional analyses support release factor-like MTRF1 as a protein able to decode nonstandard stop codons beginning with adenine in vertebrate mitochondria. RNA (New York, N.Y.), 16(6), 1146-55. PMID: 20421313

Soleimanpour-Lichaei HR, Kühl I, Gaisne M, Passos JF, Wydro M, Rorbach J, Temperley R, Bonnefoy N, Tate W, Lightowlers R.... (2007) mtRF1a is a human mitochondrial translation release factor decoding the major termination codons UAA and UAG. Molecular cell, 27(5), 745-57. PMID: 17803939

Temperley R, Richter R, Dennerlein S, Lightowlers RN, & Chrzanowska-Lightowlers ZM. (2010) Hungry codons promote frameshifting in human mitochondrial ribosomes. Science (New York, N.Y.), 327(5963), 301. PMID: 20075246

February 3, 2011
09:50 AM
904 views

Jet-lagged? it is in your blood

by Vasili Hauryliuk in stringent response

We, animals, have inbuilt metronomes with roughly 24 hour oscillation period, called circadian clocks. These clocks allow organisms to be in sync with the day / night cycle.And it turnes out that human red blood cells have a circadian clock of their own! And it keeps on ticking when the blood outside the body!Peroxiredoxins comprise a conserved family of antioxidant proteins, and researchers checked for peroxiredoxin SO2/3 oxidation level in human red blood cell samples over ........ Read more »

O'Neill JS, & Reddy AB. (2011) Circadian clocks in human red blood cells. Nature, 469(7331), 498-503. PMID: 21270888

February 1, 2011
12:02 PM
1,238 views

ppGpp mediates cross-talk between the stringent and acid stress responses

by Vasili Hauryliuk in stringent response

We know that stringent response alarmone ppGpp can do about anything, interacting with RNA Polymerase, translational GTPases, polynucleotide phosphorylase, DnaG primase, IMP dehydrogenase and adenylosuccinate synthetase to name a few. In general the result is: production of ribosomes and tRNAs is halted, cell cycle is arrested, and amino acids produced.Well, now one more target was discovered, lysine decarboxylase Ldc1/CadA. Lysine decarboxylase is induced upon acid stress conditions and protect........ Read more »

Kanjee U, Gutsche I, Alexopoulos E, Zhao B, El Bakkouri M, Thibault G, Liu K, Ramachandran S, Snider J, Pai EF.... (2011) Linkage between the bacterial acid stress and stringent responses: the structure of the inducible lysine decarboxylase. The EMBO journal. PMID: 21278708

January 18, 2011
11:04 PM
1,085 views

Z-RNA–binding domain Zα as ribosomal inhibitor: fishing for ribosomes

by Vasili Hauryliuk in stringent response

Feng at al. in NSMB show that Z-RNA (or DNA) binding domain Zα inhibits ribosomal function. Binds to the ribosome and inhibits it! Basically does what ribosome-binding antibiotics do - they bind, freeze the ribosome in some particular conformation and thus inhibit it. Viomycin can be a gerat example of that.Better still, Zα seems to bind ribosomes nondiscriminantly (both bacterial and mammalian), so using a column with immobilized Zα you could purify ribosomes from whatever cel........ Read more »

Feng S, Li H, Zhao J, Pervushin K, Lowenhaupt K, Schwartz TU, & Dröge P. (2011) Alternate rRNA secondary structures as regulators of translation. Nature structural . PMID: 21217697

Ermolenko DN, Spiegel PC, Majumdar ZK, Hickerson RP, Clegg RM, & Noller HF. (2007) The antibiotic viomycin traps the ribosome in an intermediate state of translocation. Nature structural , 14(6), 493-7. PMID: 17515906

January 17, 2011
11:12 AM
1,093 views

Darwin meets Gibbs: thermodynamics of natural selection

by Vasili Hauryliuk in stringent response

In order to perform its function, protein should be properly folded. Therefore stability of this proteins’ native state is crucial for its function. Denatured protein can be toxic the cell and requires specialised machinery to degrade it, thus compromising cells fitness. Having a denatured protein is not equal to just not having a functional one, it is equal to not having a functional one and hiving some costly junk.Since stability is so crucial for proteins function, it must leave its trace i........ Read more »

Fu H, Grimsley G, Scholtz JM, & Pace CN. (2010) Increasing protein stability: importance of DeltaC(p) and the denatured state. Protein science : a publication of the Protein Society, 19(5), 1044-52. PMID: 20340133

Franzosa EA, & Xia Y. (2009) Structural determinants of protein evolution are context-sensitive at the residue level. Molecular biology and evolution, 26(10), 2387-95. PMID: 19597162

Drummond DA, & Wilke CO. (2008) Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution. Cell, 134(2), 341-52. PMID: 18662548

Geiler-Samerotte KA, Dion MF, Budnik BA, Wang SM, Hartl DL, & Drummond DA. (2011) Misfolded proteins impose a dosage-dependent fitness cost and trigger a cytosolic unfolded protein response in yeast. Proceedings of the National Academy of Sciences of the United States of America, 108(2), 680-5. PMID: 21187411

Loladze VV, Ermolenko DN, & Makhatadze GI. (2001) Heat capacity changes upon burial of polar and nonpolar groups in proteins. Protein science : a publication of the Protein Society, 10(7), 1343-52. PMID: 11420436

DePristo MA, Weinreich DM, & Hartl DL. (2005) Missense meanderings in sequence space: a biophysical view of protein evolution. Nature reviews. Genetics, 6(9), 678-87. PMID: 16074985

January 15, 2011
06:24 AM
954 views

Methicillin-resistant S. aureus (MRSA) JKD6229, freaking out and deadly

by Vasili Hauryliuk in stringent response

Stringent response, as I wrote here, here, and here, and here, is a central regulator of bacterial physiology, which decides whether to grow happily churning out new proteins without a care or to shut down all of the unnecessary systems, relocate all resources to amino acid production and put up a fight. So what happens if a mutation hyper-activates it in Staphylococcus aureus? Wonder no more - the pathogen goes berserk!The strain in question is call........ Read more »

Gao W, Chua K, Davies JK, Newton HJ, Seemann T, Harrison PF, Holmes NE, Rhee HW, Hong JI, Hartland EL.... (2010) Two novel point mutations in clinical Staphylococcus aureus reduce linezolid susceptibility and switch on the stringent response to promote persistent infection. PLoS pathogens, 6(6). PMID: 20548948

Dalebroux ZD, Svensson SL, Gaynor EC, & Swanson MS. (2010) ppGpp conjures bacterial virulence. Microbiology and molecular biology reviews : MMBR, 74(2), 171-99. PMID: 20508246

Mittenhuber G. (2001) Comparative genomics and evolution of genes encoding bacterial (p)ppGpp synthetases/hydrolases (the Rel, RelA and SpoT proteins). Journal of molecular microbiology and biotechnology, 3(4), 585-600. PMID: 11545276

Escaich S. (2010) Novel agents to inhibit microbial virulence and pathogenicity. Expert opinion on therapeutic patents, 20(10), 1401-18. PMID: 20718591

January 14, 2011
01:18 PM
881 views

Ribosome-assisted protein UN-folding

by Vasili Hauryliuk in stringent response

"Stand still, do not move! I gave you life, I will also kill you!" said Taras, and, retreating a step backwards, he brought his gun up to his shoulder. Andrii was white as a sheet; his lips moved gently, and he uttered a name; but it was not the name of his native land, nor of his mother, nor his brother; it was the name of the beautiful Pole. Taras fired.Taras Bulba, Nikolai Vasilievich GogolRibosome makes proteins, we all know that. But producing a string of amino acids is just a half it. In o........ Read more »

O'Brien EP, Christodoulou J, Vendruscolo M, & Dobson CM. (2011) New Scenarios of Protein Folding Can Occur on the Ribosome. Journal of the American Chemical Society. PMID: 21204555

January 13, 2011
01:17 PM
1,381 views

Playing chicken, single molecule

by Vasili Hauryliuk in stringent response

Many things happen to DNA. Proteins bind, slide along, dissociate. Sometimes they bump into each other, and then... what happens then?This was exactly the question adressed in Finkelstein at al, Nature 2010. They were particularly interested in a bacterial protein called RecBCD, which is a powerful helicase. Using single-molecule microscopy theyhad a look at what happens when RecBCD rams into some other protein.And they had several to look at. RNA polymerase was the........ Read more »

Finkelstein IJ, Visnapuu ML, & Greene EC. (2010) Single-molecule imaging reveals mechanisms of protein disruption by a DNA translocase. Nature, 468(7326), 983-7. PMID: 21107319

January 9, 2011
06:08 AM
1,045 views

You pay in ribosomes for proteins

by Vasili Hauryliuk in stringent response

Everything costs. When cell grows, it needs energy and in needs materials. By the end of the day it comes down to accounting: if you need to make N proteins, you will need X ATPs molecules, Y aminoacids and Z ribosomes to do the job. And of all these ribosomes are the most expensive to make: they are huge, made of RNA and if you want to make proteins fast, you need lots of ribosomes!So research team led by famous systems biologist Uri Alon decided to quantify the cost of making a protein. In ord........ Read more »

Shachrai I, Zaslaver A, Alon U, & Dekel E. (2010) Cost of unneeded proteins in E. coli is reduced after several generations in exponential growth. Molecular cell, 38(5), 758-67. PMID: 20434381

Potrykus K, & Cashel M. (2008) (p)ppGpp: still magical?. Annual review of microbiology, 35-51. PMID: 18454629

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Vasili Hauryliuk

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