RT Journal Article
SR Electronic
T1 How do metal ions direct ribozyme folding?
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 037895
DO 10.1101/037895
A1 Natalia A. Denesyuk
A1 D. Thirumalai
YR 2016
UL http://biorxiv.org/content/early/2016/01/26/037895.abstract
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.