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.
Department of Biochemistry, Stanford University, Stanford, California 94305, USA.
Sergey V
SV
Solomatin
Max
M
Greenfeld
Steven
S
Chu
Daniel
D
Herschlag
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