Differential conformational dynamics in two type-A RNA-binding domains drive the double-stranded RNA recognition and...

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Trans-activation response (TAR) RNA-binding protein (TRBP) is crucial for RNA interference (RNAi).
• TRBP interacts with various pre-microRNAs (miRNAs) and small interfering RNAs (siRNAs).
• TRBP's ability to bind diverse RNA structures suggests dynamic adaptability.

Purpose of the Study:

• To investigate the intrinsic and RNA-induced conformational dynamics of TRBP's double-stranded RNA-binding domain 2 (dsRBD2).
• To compare the dynamics of dsRBD2 with previously studied dsRBD1.
• To understand the role of protein dynamics in TRBP's RNA recognition and binding versatility.

Main Methods:

• Computational analysis of TRBP-dsRBD2 intrinsic and RNA-induced conformational dynamics.
• Comparative analysis with existing dsRBD1 dynamics data.
• Development of a dynamics-driven model for TRBP's tandem dsRNA-binding domains.

Main Results:

• TRBP dsRBD1 and dsRBD2 exhibit differential binding affinities to dsRNA due to unique residues and structural plasticity.
• dsRBD2 displays more constrained conformational plasticity compared to dsRBD1.
• RNA binding induces conformational exchange in dsRBD2, but with less amplitude than in dsRBD1.

Conclusions:

• TRBP's tandem dsRBDs possess distinct dynamic properties that contribute to their RNA-binding versatility.
• The differential dynamics of dsRBD1 and dsRBD2 are key to accommodating heterogeneous target RNA structures.
• A dynamics-driven model explains how TRBP achieves broad dsRNA recognition.