Multiple native states reveal persistent ruggedness of an RNA folding landscape

Sergey V Solomatin ¹, Max Greenfeld , Steven Chu

⁰Department of Biochemistry, Stanford University, Stanford, California 94305, USA.

Nature +

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February 5, 2010

View abstract on PubMed

Summary

Biological macromolecules like RNA can fold into multiple distinct native states, challenging the traditional view of a single energy minimum. This ruggedness in RNA folding landscapes affects active conformations.

Area Of Science

Biochemistry
Molecular Biology
Structural Biology

Background

The thermodynamic hypothesis posits that a macromolecule's sequence dictates a unique native structure as the global energy minimum.
Complex folding landscapes for large macromolecules raise questions about the existence of multiple stable, active conformations beyond a single global minimum.
While some proteins follow two-state folding models, evidence suggests more complex landscapes with interconverting active states.

Purpose Of The Study

To investigate the folding landscape topology of RNA enzymes using single-molecule experiments.
To determine if RNA enzymes fold into multiple distinct native states.
To assess the timescale of interconversion between these native states.

Main Methods

Utilized single-molecule experiments to probe RNA folding dynamics.
Analyzed the conformational landscape of an RNA enzyme.

Main Results

Demonstrated that an RNA enzyme folds into multiple distinct native states.
Showed that interconversion between these native states occurs on a timescale significantly longer than catalysis.
Provided evidence for ruggedness in RNA folding landscapes extending to native conformational space.

Conclusions

RNA folding landscapes are complex and rugged, extending into the conformational space of native states.
The existence of multiple, slowly interconverting native states challenges simplified models of macromolecular folding.
This finding has implications for understanding RNA function and evolution.

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