Conformational stability of PCID2 upon DSS1 binding with molecular dynamics simulation.

Area of Science:

• Molecular Biology
• Biochemistry
• Structural Biology

Background:

• The intrinsically disordered protein (IDP) DSS1 interacts with PCID2 TREX-2.
• The DSS1-PCID2 complex is crucial for mRNA export.
• The precise binding mechanism between DSS1 and PCID2 remains unclear.

Purpose of the Study:

• To elucidate the molecular mechanisms governing the binding of DSS1 to PCID2.
• To compare the conformational dynamics of PCID2 in its apo and DSS1-bound states.

Main Methods:

• Three independent 500-ns molecular dynamics (MD) simulations were conducted.
• Comparative analysis of apo-PCID2 and DSS1-bound PCID2 conformational variations.
• Binding free energy decomposition analysis.

Main Results:

• DSS1 binding reduces PCID2 conformational flexibility, particularly in helices IV and VIII.
• Increased coil formation between helices III and IV and formation of an anti-parallel β-sheet in PCID2 upon DSS1 binding.
• Electrostatic and hydrophobic interactions are critical for DSS1-PCID2 recognition, with a seven-residue hydrophobic core in DSS1 being significant.

Conclusions:

• DSS1 binding induces specific structural changes in PCID2, facilitating complex formation.
• Hydrophobic and electrostatic interactions are key drivers of the DSS1-PCID2 binding interface.
• The study provides a framework for understanding IDP-partner recognition mechanisms.