PT  - JOURNAL ARTICLE
AU  - Natalia A. Denesyuk
AU  - D. Thirumalai
TI  - How do metal ions direct ribozyme folding?
AID  - 10.1101/037895
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 037895
4099  - http://biorxiv.org/content/early/2016/01/26/037895.short
4100  - http://biorxiv.org/content/early/2016/01/26/037895.full
AB  - 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.