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 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.
Baird
Nathan J
NJ
Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.
Westhof
Eric
E
Qin
Hong
H
Pan
Tao
T
Sosnick
Tobin R
TR
D001412:Bacillus subtilis / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043262:Ribonuclease P / Q000235:genetics; D013816:Thermodynamics
D012329:RNA, Bacterial; D012313:RNA; D043262:Ribonuclease P; D008274:Magnesium