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bioRxiv · 10.1101/037895

How do metal ions direct ribozyme folding?

Dave Thirumalai·Natasha A. Denesyuk
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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 which 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 coordination of Mg2+ ions to specific nucleotides. However, competition for scarce Mg2+ and topological constraints arising from chain connectivity prevent 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.

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Dave Thirumalai, Natasha A. Denesyuk. 2016-01-26. How do metal ions direct ribozyme folding?. https://doi.org/10.1101/037895

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