Spontaneous adjustment mechanism in an RNA-binding protein: cooperation between energetic stabilization and target search enhancement.
We propose a novel concept associated with the relationship between structure and function in biomolecular systems. We performed a 75 nanoseconds molecular dynamics (MD) simulation for an RNA-binding protein, neuro-oncological ventral antigen (NOVA), and examined its physico-chemical properties. NOVA dissociated from the NOVA-RNA complex showed a large conformational change: formation of intra-molecular hydrogen bonds between the C-terminal region and the loop structure located at the middle of amino acid sequence. The free energy analysis suggests that the deformed structure is more stabilized in macromolecular crowding environment where the dielectric constant is smaller than 5. The solvent accessible surface area (SASA) analysis indicates that NOVA enhances the efficiency of association with RNA by changing the relative SASA for the target sequence in RNA molecules. Based on the obtained results, we propose a novel concept of spontaneous adjustment mechanism to explain the structural and energetic changes observed for NOVA in the free state.
Kurisaki
Ikuo
I
Graduate School of Engineering, Kobe University, 1-1, Rokkodai, Nada, Kobe 657-8501, Japan. kurisaki@insilico.h.kobe-u.ac.jp
Watanabe
Hirofumi
H
Tanaka
Shigenori
S
D000595:Amino Acid Sequence; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D000090682:Neuro-Oncological Ventral Antigen; D011485:Protein Binding; D011487:Protein Conformation; D016601:RNA-Binding Proteins / Q000737:chemistry*; D013816:Thermodynamics
C406163:NOVA2 protein, human; D009419:Nerve Tissue Proteins; D000090682:Neuro-Oncological Ventral Antigen; D016601:RNA-Binding Proteins