Phosphorylation drives a dynamic switch in serine/arginine-rich proteins

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Serine/arginine-rich (SR) proteins are crucial for RNA metabolism.
• These proteins are extensively phosphorylated on serine residues within RS repeats.

Purpose of the Study:

• To investigate the structural and dynamic impact of phosphorylation on SR protein RS domains.
• To elucidate the molecular mechanism underlying SR protein function and regulation.

Main Methods:

• Nuclear magnetic resonance (NMR) spectroscopy.
• Molecular dynamics (MD) simulations.
• Analysis of serine/arginine-rich splicing factor 1 and hPrp28.

Main Results:

• Phosphorylation induces a conformational switch in SR protein RS domains, transitioning from a disordered to a partially rigidified arch-like structure.
• This switch is dependent on phosphate charge and reduces conformational entropy.
• A similar dynamic switch was observed in the SR-related protein hPrp28, essential for spliceosome assembly.

Conclusions:

• A phosphorylation-induced dynamic switch is a common feature of serine/arginine-rich proteins.
• This mechanism explains the functional redundancy and the significant impact of RS domain phosphorylation on protein interactions and RNA binding.