Global RNA Fold and Molecular Recognition for a pfl Riboswitch Bound to ZMP, a Master Regulator of One-Carbon Metabolism

Journal Article · Sat Aug 01 00:00:00 EDT 2015 · Structure

DOI:https://doi.org/10.1016/j.str.2015.05.016· OSTI ID:1433725

Ren, Aiming; Rajashankar, Kanagalaghatta R.; Patel, Dinshaw J.

ZTP, the pyrophosphorylated analog of ZMP (5- amino-4-imidazole carboxamide ribose-5'-monophosphate), was identified as an alarmone that senses 10-formyl-tetrahydroflate deficiency in bacteria. Recently, a pfl riboswitch was identified that selectively binds ZMP and regulates genes associated with purine biosynthesis and one-carbon metabolism. Here we report on the structure of the ZMP-bound Thermosinus carboxydivorans pfl riboswitch sensing domain, thereby defining the pseudoknot-based tertiary RNA fold, the binding-pocket architecture, and principles underlying ligand recognition specificity. Molecular recognition involves shape complementarity, with the ZMP 5-amino and carboxamide groups paired with the Watson-Crick edge of an invariant uracil, and the imidazole ring sandwiched between guanines, while the sugar hydroxyls form intermolecular hydrogen bond contacts. The burial of the ZMP base and ribose moieties, together with unanticipated coordination of the carboxamide by Mg²⁺, contrasts with exposure of the 5'-phosphate to solvent. Lastly, our studies highlight the principles underlying RNA-based recognition of ZMP, a master regulator of one-carbon metabolism.

• Research Organization: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE Office of Science (SC); National Institutes of Health (NIH)
• Grant/Contract Number: AC02-06CH11357; S10 RR029205; P41 GM103403
• OSTI ID: 1433725
• Alternate ID(s): OSTI ID: 1209696
• Journal Information: Structure, Journal Name: Structure Vol. 23 Journal Issue: 8; ISSN 0969-2126
• Publisher: Elsevier
• Country of Publication: United Kingdom
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY