The key role of electrostatic interactions in the induced folding in RNA recognition by DCL1-A

ZHAO, LINGCI; RASIA, RODOLFO M.; GAUTO, DIEGO F.; SUAREZ, IRINA P.; WANG, JIN

PHYSICAL CHEMISTRY CHEMICAL PHYSICS

ROYAL SOC CHEMISTRY

Año: 2018 vol. 20 p. 9376 - 9388

1463-9076

The intrinsically disordered protein domain DCL1-A is the first report of a complete double stranded RNA binding domain folding upon binding. DCL1-A recognizes the dsRNA by acquiring a well-folded structure after engagement with its interaction partner. Despite the structural characterization of the interaction complex underlying the recognition of dsRNA has been established, the dynamics of disorder-to-order transitions in the binding process remains elusive. Here we have developed a coarse-grained structure-based model with consideration of electrostatic interactions to explore the mechanism of the coupled folding and binding. Our approach led to remarkable agreements with both experimental and theoretical results. We quantified the global binding-folding landscape, which indicates a synergistic binding induced folding mechanism. We further investigated the effect of electrostatic interactions in this coupled folding and binding process. It reveals that non-native electrostatic interactions dominate the initial stage of the recognition. Our results help improve our understanding of the induced folding of the IDP DCL1-A upon binding to dsRNA. Such methods developed here can be applied for further explorations of the dynamics of coupled folding and binding systems.