Multiple native states reveal persistent ruggedness of an RNA folding landscape.
According to the 'thermodynamic hypothesis', the sequence of a biological macromolecule defines its folded, active (or 'native') structure as a global energy minimum in the folding landscape. However, the enormous complexity of folding landscapes of large macromolecules raises the question of whether there is in fact a unique global minimum corresponding to a unique native conformation or whether there are deep local minima corresponding to alternative active conformations. The folding of many proteins is well described by two-state models, leading to highly simplified representations of protein folding landscapes with a single native conformation. Nevertheless, accumulating experimental evidence suggests a more complex topology of folding landscapes with multiple active conformations that can take seconds or longer to interconvert. Here we demonstrate, using single-molecule experiments, that an RNA enzyme folds into multiple distinct native states that interconvert on a timescale much longer than that of catalysis. These data demonstrate that severe ruggedness of RNA folding landscapes extends into conformational space occupied by native conformations.
Solomatin
Sergey V
SV
Department of Biochemistry, Stanford University, Stanford, California 94305, USA.
Greenfeld
Max
M
Chu
Steven
S
Herschlag
Daniel
D
D001483:Base Sequence; D055162:Biocatalysis; D031541:Fluorescence Resonance Energy Transfer; D007438:Introns / Q000235:genetics; D007700:Kinetics; D009690:Nucleic Acid Conformation; D009843:Oligoribonucleotides / Q000235:genetics / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry* / Q000378:metabolism*; D013768:Tetrahymena / Q000201:enzymology / Q000235:genetics*; D013816:Thermodynamics; D013997:Time Factors
D009843:Oligoribonucleotides; D016337:RNA, Catalytic