Structural insights into RapZ-mediated regulation of bacterial amino-sugar metabolism
Nucleic Acids Research
Oxford University Press
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Gonzalez, G., Durica-Mitic, S., Hardwick, S., Moncrieffe, M., Resch, M., Neumann, P., Ficner, R., et al. (2017). Structural insights into RapZ-mediated regulation of bacterial amino-sugar metabolism. Nucleic Acids Research https://doi.org/10.1093/nar/gkx732
In phylogenetically diverse bacteria, the conserved protein RapZ plays a central role in RNA-mediated regulation of amino-sugar metabolism. RapZ contributes to the control of glucosamine phosphate biogenesis by selectively presenting the regulatory small RNA GlmZ to the essential ribonuclease RNase E for inactivation. Here, we report the crystal structures of full length Escherichia coli RapZ at 3.40 Å and 3.25 Å, and its isolated C-terminal domain at 1.17 Å resolution. The structural data confirm that the N-terminal domain of RapZ possesses a kinase fold, whereas the C-terminal domain bears closest homology to a subdomain of 6-phosphofructokinase, an important enzyme in the glycolytic pathway. RapZ self-associates into a domain swapped dimer of dimers, and in vivo data support the importance of quaternary structure in RNA-mediated regulation of target gene expression. Based on biochemical, structural and genetic data, we suggest a mechanism for binding and presentation by RapZ of GlmZ and the closely related decoy sRNA, GlmY. We discuss a scenario for the molecular evolution of RapZ through re-purpose of enzyme components from central metabolism.
metabolism, amino sugars, endoribonucleases, phosphates, phosphotransferases, bacteria, enzymes, glucosamine, ribonucleases, rna, escherichia coli, crystal structure, dimers
This work was supported by the Wellcome Trust [RG84381 to B.F.L]; and the Austrian Science Fund [P 26681-B22 and F4317 to B.G.]. GMG was supported by a Gates Cambridge Scholarship. Funding for open access charge: Wellcome Trust.
Wellcome Trust (094229/Z/10/Z)
Wellcome Trust (200873/Z/16/Z)
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External DOI: https://doi.org/10.1093/nar/gkx732
This record's URL: https://www.repository.cam.ac.uk/handle/1810/267669
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International