title: How do metal ions direct ribozyme folding?
abstract: Ribozymes, which carry out phosphoryl-transfer reactions, often require Mg(2+) 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 Mg(2+) concentrations, and are transiently stabilized by the coordination of Mg(2+) ions to specific nucleotides. However, competition for scarce Mg(2+) and topological constraints that arise from chain connectivity prevent the complete folding of the ribozyme. A much higher Mg(2+) concentration is required for complete folding of the ribozyme and stabilization of the active site. When Mg(2+) is replaced by Ca(2+) 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.
authors.affiliation: Institute for Physical Science and Technology, University of Maryland, College Park, Maryland 20742, USA.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Denesyuk
authors.affiliation: Institute for Physical Science and Technology, University of Maryland, College Park, Maryland 20742, USA.|Department of Chemistry and Biochemistry and Biophysics Program, University of Maryland, College Park, Maryland 20742, USA.
authors.forename: D
authors.initials: D
authors.lastname: Thirumalai
mesh_terms: D001483:Base Sequence; D008274:Magnesium / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017510:Protein Folding; D016337:RNA, Catalytic / Q000737:chemistry*
chemical_list: D016337:RNA, Catalytic; D008274:Magnesium