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A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography.

Bunker RD, Mandal K, Bashiri G, Chaston JJ, Pentelute BL, Lott JS, Kent SB, Baker EN
Proc Natl Acad Sci U S A 112 4310-5 (2015)
Cited: 21 times
EuropePMC logo PMID: 25831534

Abstract

Protein 3D structure can be a powerful predictor of function, but it often faces a critical roadblock at the crystallization step. Rv1738, a protein from Mycobacterium tuberculosis that is strongly implicated in the onset of nonreplicating persistence, and thereby latent tuberculosis, resisted extensive attempts at crystallization. Chemical synthesis of the L- and D-enantiomeric forms of Rv1738 enabled facile crystallization of the D/L-racemic mixture. The structure was solved by an ab initio approach that took advantage of the quantized phases characteristic of diffraction by centrosymmetric crystals. The structure, containing L- and D-dimers in a centrosymmetric space group, revealed unexpected homology with bacterial hibernation-promoting factors that bind to ribosomes and suppress translation. This suggests that the functional role of Rv1738 is to contribute to the shutdown of ribosomal protein synthesis during the onset of nonreplicating persistence of M. tuberculosis.

Articles - 4wsp mentioned but not cited (1)

  1. A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography. Bunker RD, Mandal K, Bashiri G, Chaston JJ, Pentelute BL, Lott JS, Kent SB, Baker EN. Proc Natl Acad Sci U S A 112 4310-4315 (2015)


Reviews citing this publication (7)

  1. Mycobacterial Dormancy Systems and Host Responses in Tuberculosis. Peddireddy V, Doddam SN, Ahmed N. Front Immunol 8 84 (2017)
  2. Novel protein science enabled by total chemical synthesis. Kent SBH. Protein Sci 28 313-328 (2019)
  3. Regulation of Three Virulence Strategies of Mycobacterium tuberculosis: A Success Story. Zondervan NA, van Dam JCJ, Schaap PJ, Martins Dos Santos VAP, Suarez-Diez M. Int J Mol Sci 19 E347 (2018)
  4. Translational regulation in mycobacteria and its implications for pathogenicity. Sawyer EB, Grabowska AD, Cortes T. Nucleic Acids Res 46 6950-6961 (2018)
  5. Aligator: A computational tool for optimizing total chemical synthesis of large proteins. Jacobsen MT, Erickson PW, Kay MS. Bioorg Med Chem 25 4946-4952 (2017)
  6. Synthesis and applications of mirror-image proteins. Harrison K, Mackay AS, Kambanis L, Maxwell JWC, Payne RJ. Nat Rev Chem 7 383-404 (2023)
  7. Ribosome profiling enhances understanding of mycobacterial translation. Sawyer EB, Cortes T. Front Microbiol 13 976550 (2022)

Articles citing this publication (13)

  1. The Complete Structure of the Mycobacterium smegmatis 70S Ribosome. Hentschel J, Burnside C, Mignot I, Leibundgut M, Boehringer D, Ban N. Cell Rep 20 149-160 (2017)
  2. A snapshot of translation in Mycobacterium tuberculosis during exponential growth and nutrient starvation revealed by ribosome profiling. Sawyer EB, Phelan JE, Clark TG, Cortes T. Cell Rep 34 108695 (2021)
  3. Activity-Based Protein Profiling Reveals That Cephalosporins Selectively Active on Non-replicating Mycobacterium tuberculosis Bind Multiple Protein Families and Spare Peptidoglycan Transpeptidases. Lopez Quezada L, Smith R, Lupoli TJ, Edoo Z, Li X, Gold B, Roberts J, Ling Y, Park SW, Nguyen Q, Schoenen FJ, Li K, Hugonnet JE, Arthur M, Sacchettini JC, Nathan C, Aubé J. Front Microbiol 11 1248 (2020)
  4. Subunit Vaccines Consisting of Antigens from Dormant and Replicating Bacteria Show Promising Therapeutic Effect against Mycobacterium Bovis BCG Latent Infection. Li F, Kang H, Li J, Zhang D, Zhang Y, Dannenberg AM, Liu X, Niu H, Ma L, Tang R, Han X, Gan C, Ma X, Tan J, Zhu B. Scand J Immunol 85 425-432 (2017)
  5. Crystallization of Enantiomerically Pure Proteins from Quasi-Racemic Mixtures: Structure Determination by X-Ray Diffraction of Isotope-Labeled Ester Insulin and Human Insulin. Mandal K, Dhayalan B, Avital-Shmilovici M, Tokmakoff A, Kent SB. Chembiochem 17 421-425 (2016)
  6. Reinvestigation of the biological activity of d-allo-ShK protein. Dang B, Chhabra S, Pennington MW, Norton RS, Kent SBH. J Biol Chem 292 12599-12605 (2017)
  7. A crystal-structural study of Pauling-Corey rippled sheets. Kuhn AJ, Ehlke B, Johnstone TC, Oliver SRJ, Raskatov JA. Chem Sci 13 671-680 (2022)
  8. Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations. Wang Y, Han L, Yuan N, Wang H, Li H, Liu J, Chen H, Zhang Q, Dong S. Chem Sci 9 1940-1946 (2018)
  9. A Phenotypic Characterization of Two Isolates of a Multidrug-Resistant Outbreak Strain of Mycobacterium tuberculosis with Opposite Epidemiological Fitness. Bei J, Bigi MM, Lima A, Zhang Q, Blanco FC, Lopez B, Yu T, Wang Z, Dai Z, Chen Z, Cataldi AA, Sasiain MDC, Ritacco V, De la Barrera S, Soria MA, Durán R, Bigi F. Biomed Res Int 2020 4741237 (2020)
  10. Racemic crystal structures of peptide toxins, GsMTx4 prepared by protein total synthesis. Qu Q, Gao S, Li YM. J Pept Sci 24 e3112 (2018)
  11. Toll-like receptor-mediated innate immune responses by recognition of the recombinant dormancy-associated Mycobacterium tuberculosis proteins Rv2659c and Rv1738. Saelee C, Hanthamrongwit J, Soe PT, Khaenam P, Inthasin N, Ekpo P, Chootong P, Leepiyasakulchai C. PLoS One 17 e0273517 (2022)
  12. Transcriptional Biomarkers of Differentially Detectable Mycobacterium tuberculosis in Patient Sputum. Zainabadi K, Saito K, Mishra S, Walsh KF, Mathurin LD, Vilbrun SC, Ocheretina O, Pape JW, Fitzgerald DW, Nathan CF, Lee MH. mBio 13 e0270122 (2022)
  13. The rippled β-sheet layer configuration-a novel supramolecular architecture based on predictions by Pauling and Corey. Hazari A, Sawaya MR, Vlahakis N, Johnstone TC, Boyer D, Rodriguez J, Eisenberg D, Raskatov JA. Chem Sci 13 8947-8952 (2022)


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