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Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
Published on: July 16, 2017
Conformational stability of PCID2 upon DSS1 binding with molecular dynamics simulation
Qianjun Liu1, Guodong Hu, Zanxia Cao
1Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, College of Physics and Electronic Information, Dezhou University, Dezhou, 253023, China.
Abstract:
DSS1 is a small acidic intrinsically disordered protein (IDP) that can fold upon binding with PCID2 TREX-2. The resulting complex plays a key role in mRNA export. However, the binding mechanism between DSS1 and PCID2 is unsolved. Here, three independent 500-ns molecular dynamics (MD) simulations were performed to study the DSS1-PCID2 binding mechanism by comparing apo-PCID2 and bound PCID2. The results show that the conformational variation of bound PCID2 is smaller than that of apo-PCID2, especially in the binding domain of two helices (helix IV and VIII). The probability of coil formation between helix III and helix IV of bound PCID2 increases, and a short anti-parallel β-sheet forms upon DSS1 binding. The decomposition of binding free energy into protein and residue pairs suggests that electrostatic and hydrophobic interactions play key roles in the recognition between DSS1 and PCID2. There is a hydrophobic core of seven residues in DSS1 favorable to the binding of PCID2. These analytical methods can be used to reveal the recognition mechanisms of other IDPs and their partners.
Insights
The binding mechanism between intrinsically disordered protein DSS1 and PCID2 TREX-2 was investigated. Molecular dynamics simulations revealed key electrostatic and hydrophobic interactions driving their complex formation for mRNA export.
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.
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