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preLekára.sk / Odborné časopisy / PLOS Genetics / 2010 - 11

Systematic Dissection and Trajectory-Scanning Mutagenesis of the Molecular Interface That Ensures Specificity of Two-Component Signaling Pathways

English version České info

Two-component signal transduction systems enable bacteria to sense and respond to a wide range of environmental stimuli. Sensor histidine kinases transmit signals to their cognate response regulators via phosphorylation. The faithful transmission of information through two-component pathways and the avoidance of unwanted cross-talk require exquisite specificity of histidine kinase-response regulator interactions to ensure that cells mount the appropriate response to external signals. To identify putative specificity-determining residues, we have analyzed amino acid coevolution in two-component proteins and identified a set of residues that can be used to rationally rewire a model signaling pathway, EnvZ-OmpR. To explore how a relatively small set of residues can dictate partner selectivity, we combined alanine-scanning mutagenesis with an approach we call trajectory-scanning mutagenesis, in which all mutational intermediates between the specificity residues of EnvZ and another kinase, RstB, were systematically examined for phosphotransfer specificity. The same approach was used for the response regulators OmpR and RstA. Collectively, the results begin to reveal the molecular mechanism by which a small set of amino acids enables an individual kinase to discriminate amongst a large set of highly-related response regulators and vice versa. Our results also suggest that the mutational trajectories taken by two-component signaling proteins following gene or pathway duplication may be constrained and subject to differential selective pressures. Only some trajectories allow both the maintenance of phosphotransfer and the avoidance of unwanted cross-talk.

Vyšlo v časopise: Systematic Dissection and Trajectory-Scanning Mutagenesis of the Molecular Interface That Ensures Specificity of Two-Component Signaling Pathways. PLoS Genet 6(11): e32767. doi:10.1371/journal.pgen.1001220
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001220

Souhrn

Two-component signal transduction systems enable bacteria to sense and respond to a wide range of environmental stimuli. Sensor histidine kinases transmit signals to their cognate response regulators via phosphorylation. The faithful transmission of information through two-component pathways and the avoidance of unwanted cross-talk require exquisite specificity of histidine kinase-response regulator interactions to ensure that cells mount the appropriate response to external signals. To identify putative specificity-determining residues, we have analyzed amino acid coevolution in two-component proteins and identified a set of residues that can be used to rationally rewire a model signaling pathway, EnvZ-OmpR. To explore how a relatively small set of residues can dictate partner selectivity, we combined alanine-scanning mutagenesis with an approach we call trajectory-scanning mutagenesis, in which all mutational intermediates between the specificity residues of EnvZ and another kinase, RstB, were systematically examined for phosphotransfer specificity. The same approach was used for the response regulators OmpR and RstA. Collectively, the results begin to reveal the molecular mechanism by which a small set of amino acids enables an individual kinase to discriminate amongst a large set of highly-related response regulators and vice versa. Our results also suggest that the mutational trajectories taken by two-component signaling proteins following gene or pathway duplication may be constrained and subject to differential selective pressures. Only some trajectories allow both the maintenance of phosphotransfer and the avoidance of unwanted cross-talk.

Zdroje

1. SchwartzMA

MadhaniHD

2004 Principles of MAP kinase signaling specificity in Saccharomyces cerevisiae. Annu Rev Genet 38 725 748

2. UbersaxJA

FerrellJEJr

2007 Mechanisms of specificity in protein phosphorylation. Nat Rev Mol Cell Biol 8 530 541

3. StockAM

RobinsonVL

GoudreauPN

2000 Two-component signal transduction. Annu Rev Biochem 69 183 215

4. GaoR

MackTR

StockAM

2007 Bacterial response regulators: versatile regulatory strategies from common domains. Trends Biochem Sci 32 225 234

5. LaubMT

GoulianM

2007 Specificity in two-component signal transduction pathways. Annu Rev Genet 41 121 145

6. SkerkerJM

PrasolMS

PerchukBS

BiondiEG

LaubMT

2005 Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis. PLoS Biol 3 e334 doi:10.1371/journal.pbio.0030334

7. FisherSL

KimSK

WannerBL

WalshCT

1996 Kinetic comparison of the specificity of the vancomycin resistance VanS for two response regulators, VanR and PhoB. Biochemistry 35 4732 4740

8. GrimshawCE

HuangS

HansteinCG

StrauchMA

BurbulysD

1998 Synergistic kinetic interactions between components of the phosphorelay controlling sporulation in Bacillus subtilis. Biochemistry 37 1365 1375

9. SkerkerJM

PerchukBS

SiryapornA

LubinEA

AshenbergO

2008 Rewiring the specificity of two-component signal transduction systems. Cell 133 1043 1054

10. WeigtM

WhiteRA

SzurmantH

HochJA

HwaT

2009 Identification of direct residue contacts in protein-protein interaction by message passing. Proc Natl Acad Sci U S A 106 67 72

11. BurgerL

van NimwegenE

2008 Accurate prediction of protein-protein interactions from sequence alignments using a Bayesian method. Mol Syst Biol 4 165

12. WhiteRA

SzurmantH

HochJA

HwaT

2007 Features of protein-protein interactions in two-component signaling deduced from genomic libraries. Methods Enzymol 422 75 101

13. CasinoP

RubioV

MarinaA

2009 Structural insight into partner specificity and phosphoryl transfer in two-component signal transduction. Cell 139 325 336

14. GloorGB

MartinLC

WahlLM

DunnSD

2005 Mutual information in protein multiple sequence alignments reveals two classes of coevolving positions. Biochemistry 44 7156 7165

15. QinL

CaiS

ZhuY

InouyeM

2003 Cysteine-scanning analysis of the dimerization domain of EnvZ, an osmosensing histidine kinase. J Bacteriol 185 3429 3435

16. OrtlundEA

BridghamJT

RedinboMR

ThorntonJW

2007 Crystal structure of an ancient protein: evolution by conformational epistasis. Science 317 1544 1548

17. CarlsonCD

WarrenCL

HauschildKE

OzersMS

QadirN

2010 Specificity landscapes of DNA binding molecules elucidate biological function. Proc Natl Acad Sci U S A 107 4544 4549

18. WeinreichDM

DelaneyNF

DepristoMA

HartlDL

2006 Darwinian evolution can follow only very few mutational paths to fitter proteins. Science 312 111 114

19. BridghamJT

OrtlundEA

ThorntonJW

2009 An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature 461 515 519

20. LunzerM

MillerSP

FelsheimR

DeanAM

2005 The biochemical architecture of an ancient adaptive landscape. Science 310 499 501

21. DorgaiL

YagilE

WeisbergRA

1995 Identifying determinants of recombination specificity: construction and characterization of mutant bacteriophage integrases. J Mol Biol 252 178 188

22. CunninghamBC

JhuraniP

NgP

WellsJA

1989 Receptor and antibody epitopes in human growth hormone identified by homolog-scanning mutagenesis. Science 243 1330 1336

23. MiyazakiK

ArnoldFH

1999 Exploring nonnatural evolutionary pathways by saturation mutagenesis: rapid improvement of protein function. J Mol Evol 49 716 720

24. BellCH

PorterSL

StrawsonA

StuartDI

ArmitageJP

2010 Using structural information to change the phosphotransfer specificity of a two-component chemotaxis signalling complex. PLoS Biol 8 e1000306 doi:10.1371/journal.pbio.1000306

25. HaldimannA

PrahaladMK

FisherSL

KimSK

WalshCT

1996 Altered recognition mutants of the response regulator PhoB: a new genetic strategy for studying protein-protein interactions. Proc Natl Acad Sci U S A 93 14361 14366

26. GrebeTW

StockJB

1999 The histidine protein kinase superfamily. Adv Microb Physiol 41 139 227

27. de HoonMJ

ImotoS

NolanJ

MiyanoS

2004 Open source clustering software. Bioinformatics 20 1453 1454

28. SaldanhaAJ

2004 Java Treeview—extensible visualization of microarray data. Bioinformatics 20 3246 3248

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Článok vyšiel v časopise

PLOS Genetics

2010 Číslo 11
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