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

Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):4310-5. doi: 10.1073/pnas.1422387112. Epub 2015 Mar 23.


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.

Keywords: Mycobacterium tuberculosis; dormancy; protein structure; racemic protein crystallography; ribosome binding.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Crystallization
  • Crystallography, X-Ray
  • Escherichia coli / metabolism
  • Humans
  • Molecular Conformation
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / metabolism
  • Peptides / chemistry
  • Protein Multimerization
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Ribosomes / chemistry
  • Stereoisomerism
  • Thermus / metabolism


  • Bacterial Proteins
  • Peptides
  • Recombinant Proteins

Associated data

  • PDB/4wpy
  • PDB/4wsp