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

作者：Bunker Richard D; Mandal Kalyaneswar; Bashiri Ghader; Chaston Jessica J; Pentelute Bradley L; Lott J Shaun; Kent Stephen B H; Baker Edward N^*

来源：Proceedings of the National Academy of Sciences, 2015, 112(14): 4310-4315.

DOI：10.1073/pnas.1422387112

• racemic protein crystallography
• Mycobacterium tuberculosis
• ribosome binding
• dormancy
• protein structure

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.

• 出版日期2015-4-7