Structure of a Folding Intermediate Reveals the Interplay Between Core and Peripheral Elements in RNA Folding

Though the molecular architecture of many native RNA structures has been characterized, the structures of folding intermediates are poorly defined. Here, we present a nucleotide-level model of a highly structured equilibrium folding intermediate of the specificity domain of the Bacillus subtilis RNa...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular biology 2005-09, Vol.352 (3), p.712-722
Main Authors: Baird, Nathan J., Westhof, Eric, Qin, Hong, Pan, Tao, Sosnick, Tobin R.
Format: Article
Language:English
Subjects:
Bacillus subtilis
Bacillus subtilis - chemistry
Bacillus subtilis - genetics
Base Sequence
Circular Dichroism
Crystallography, X-Ray
Kinetics
Magnesium - metabolism
modeling
Models, Molecular
Molecular Sequence Data
Nucleic Acid Conformation
P RNA
Ribonuclease P - genetics
RNA - chemistry
RNA - genetics
RNA - metabolism
RNA, Bacterial - chemistry
RNA, Bacterial - genetics
RNA, Bacterial - metabolism
S-domain
Thermodynamics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Though the molecular architecture of many native RNA structures has been characterized, the structures of folding intermediates are poorly defined. Here, we present a nucleotide-level model of a highly structured equilibrium folding intermediate of the specificity domain of the Bacillus subtilis RNase P RNA, obtained using chemical and nuclease mapping, circular dichroism spectroscopy, small-angle X-ray scattering and molecular modeling. The crystal structure indicates that the 154 nucleotide specificity domain is composed of several secondary and tertiary structural modules. The structure of the intermediate contains modules composed of secondary structures and short-range tertiary interactions, implying a sequential order of tertiary structure formation during folding. The intermediate lacks the native core and several long-range interactions among peripheral regions, such as a GAAA tetraloop and its receptor. Folding to the native structure requires the local rearrangement of a T-loop in the core in concert with the formation of the GAAA tetraloop–receptor interaction. The interplay of core and peripheral structure formation rationalizes the high degree of cooperativity observed in the folding transition leading to the native structure.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2005.07.010