How do metal ions direct ribozyme folding?

ABSTRACT Ribozymes, which carry out phosphoryl-transfer reactions, often require Mg2+ ions for catalytic activity. The correct folding of the active site and ribozyme tertiary structure is

also regulated by metal ions in a manner that is not fully understood. Here we employ coarse-grained molecular simulations to show that individual structural elements of the group I ribozyme

from the bacterium _Azoarcus_ form spontaneously in the unfolded ribozyme even at very low Mg2+ concentrations, and are transiently stabilized by the coordination of Mg2+ ions to specific

nucleotides. However, competition for scarce Mg2+ and topological constraints that arise from chain connectivity prevent the complete folding of the ribozyme. A much higher Mg2+

concentration is required for complete folding of the ribozyme and stabilization of the active site. When Mg2+ is replaced by Ca2+ the ribozyme folds, but the active site remains unstable.

Our results suggest that group I ribozymes utilize the same interactions with specific metal ligands for both structural stability and chemical activity. Access through your institution Buy

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Download references ACKNOWLEDGEMENTS This work was supported by a grant from the National Science Foundation (CHE 13-61946). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Institute for

Physical Science and Technology, University of Maryland, College Park, 20742, Maryland, USA Natalia A. Denesyuk & D. Thirumalai * Department of Chemistry and Biochemistry and Biophysics

Program, University of Maryland, College Park, 20742, Maryland, USA D. Thirumalai Authors * Natalia A. Denesyuk View author publications You can also search for this author inPubMed Google

Scholar * D. Thirumalai View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS N.A.D. and D.T. conceived and designed the project, analysed the

simulation data and co-wrote the paper. N.A.D. performed the simulations. CORRESPONDING AUTHOR Correspondence to D. Thirumalai. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no

competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION Supplementary information (PDF 834 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE

CITE THIS ARTICLE Denesyuk, N., Thirumalai, D. How do metal ions direct ribozyme folding?. _Nature Chem_ 7, 793–801 (2015). https://doi.org/10.1038/nchem.2330 Download citation * Received:

11 September 2014 * Accepted: 20 July 2015 * Published: 31 August 2015 * Issue Date: October 2015 * DOI: https://doi.org/10.1038/nchem.2330 SHARE THIS ARTICLE Anyone you share the following

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