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Analysis of the interactions between GMF and Arp2/3 complex in two binding sites by molecular dynamics simulation
A Popinako1, M Antonov2, D Dibrova3
1A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of RAS, 33 Leninsky Ave, bld. 2, Moscow, 119071, Russia.
Biochemical and Biophysical Research Communications
|January 18, 2018
Summary
Glia maturation factor (GMF) binds the Arp2/3 complex at two sites, revealing new mechanisms for actin filament debranching and Arp2/3 complex inactivation. This study identifies key amino acid residues stabilizing these interactions.
Area of Science:
- Cell Biology
- Biochemistry
- Structural Biology
Background:
- The Arp2/3 complex is crucial for nucleating branched actin filaments.
- Glia maturation factor (GMF) antagonizes Arp2/3 activators and promotes actin filament debranching.
Purpose of the Study:
- To comparatively analyze GMF and Arp2/3 complex interactions.
- To identify novel amino acid residues mediating GMF binding to the Arp2/3 complex.
- To elucidate the mechanism of Arp2/3 complex inactivation by GMF.
Main Methods:
- X-ray crystallography and single-particle electron microscopy (EM) for structural analysis.
- Molecular dynamics (MD) simulations, including umbrella sampling, to study binding dynamics.
- Phylogenetic and structural analyses of GMF binding sites.
Main Results:
- Identified two distinct binding sites for GMF on the Arp2/3 complex.
- Characterized quantitative and qualitative changes in hydrogen bonds upon GMF binding.
- Pinpointed specific amino acid residues in both GMF and the Arp2/3 complex that stabilize their interaction.
- Estimated the mean force profile for GMF interaction using umbrella sampling.
Conclusions:
- GMF interacts with the Arp2/3 complex at two sites, involving specific amino acid residues.
- These interactions lead to quantitative and qualitative changes in hydrogen bonding, stabilizing the complex.
- A novel mechanism for Arp2/3 complex inactivation by GMF is proposed, involving dual-site binding.
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