Conformational ensemble of an intrinsically flexible loop in mitochondrial import protein Tim21 studied by modeling and molecular dynamics simulations
| Autor: | Siqin Bala, Daisuke Kohda, Arpita Srivastava, Hajime Motomura, Osamu Miyashita, Florence Tama |
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| Rok vydání: | 2020 |
| Předmět: |
Work (thermodynamics)
Magnetic Resonance Spectroscopy Saccharomyces cerevisiae Proteins Translocase of the outer membrane Biophysics Saccharomyces cerevisiae Crystal structure Molecular Dynamics Simulation Mitochondrial Membrane Transport Proteins 01 natural sciences Biochemistry Protein Structure Secondary 03 medical and health sciences Molecular dynamics Mitochondrial Precursor Protein Import Complex Proteins 0103 physical sciences Cluster Analysis Translocase Loop modeling Molecular Biology 030304 developmental biology Physics Quantitative Biology::Biomolecules 0303 health sciences Binding Sites 010304 chemical physics biology X-Rays Energy landscape Mitochondria Loop (topology) Protein Transport Chemical physics biology.protein Carrier Proteins |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - General Subjects. 1864:129417 |
| ISSN: | 0304-4165 |
| DOI: | 10.1016/j.bbagen.2019.129417 |
| Popis: | Background Tim21, a subunit of a highly dynamic translocase of the inner mitochondrial membrane (TIM23) complex, translocates proteins by interacting with subunits in the translocase of the outer membrane (TOM) complex and Tim23 channel in the TIM23 complex. A loop segment in Tim21, which is in close proximity of the binding site of Tim23, has different conformations in X-ray, NMR and new crystal contact-free space (CCFS) structures. MD simulations can provide information on the structure and dynamics of the loop in solution. Methods The conformational ensemble of the loop was characterized using loop modeling and molecular dynamics (MD) simulations. Results MD simulations confirmed mobility of the loop. Multidimensional scaling and clustering were used to characterize the dynamic conformational ensemble of the loop. Free energy landscape showed that the CCFS crystal structure occupied a low energy region as compared to the conventional X-ray crystal structure. Analysis of crystal packing indicates that the CCFS provides larger conformational space for the motions of the loop. Conclusions Our work reported the conformational ensemble of the loop in solution, which is in agreement with the structure obtained from CCFS approach. The combination of the experimental techniques and computational methods is beneficial for studying highly flexible regions of proteins. General significance Computational methods, such as loop modeling and MD simulations, have proved to be useful for studying conformational flexibility of proteins. These methods in integration with experimental techniques such as CCFS has the potential to transform the studies on flexible regions of proteins. |
| Databáze: | OpenAIRE |
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