Effects of amino acid modifications on the permeability of the pentameric sarcolipin channel
| Autor: | Xiangfei Meng, Imshik Lee, Wei Wang, Jiana Sun, Yipeng Cao, Wenwen Zhang, Rui Yang |
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| Rok vydání: | 2020 |
| Předmět: |
Cell Membrane Permeability
Proteolipids Muscle Proteins Molecular Dynamics Simulation Biochemistry 03 medical and health sciences Molecular dynamics Structural Biology Humans Amino Acids Molecular Biology Ion channel 030304 developmental biology Ions chemistry.chemical_classification 0303 health sciences Endoplasmic reticulum 030302 biochemistry & molecular biology Water Permeation Transmembrane protein Amino acid Sarcolipin chemistry Permeability (electromagnetism) Biophysics lipids (amino acids peptides and proteins) Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Proteins: Structure, Function, and Bioinformatics. 89:427-435 |
| ISSN: | 1097-0134 0887-3585 |
| DOI: | 10.1002/prot.26028 |
| Popis: | Sarcolipin (SLN) is an important transmembrane (TM) protein encoded by long noncoding RNA. SLN is expressed in the sarcoplasmic reticulum and regulates cardiac and skeletal muscle contractions. SLN forms a pentameric hydrophobic ligand-gated ion channel. The protonation of Glu7 (protonated SLN, pSLN) and mutation of Thr18 to Ala18 (T18A) have been reported to exert a significant influence on the permeability of the channel. In this study, the altered permeability of both the pSLN and T18A pentameric channels was simulated. Combined with molecular dynamics simulation, the free-energy landscape for single ions, computational electrophysiology, diffusion coefficient, and pore geometrical characteristic analyses were performed to further understand the properties of amino acid modifications in the SLN pentameric channel. The results suggest that both the pSLN and T18A pentameric channels form stable hydrophobic ligand-gated channels. The TM voltage has a positive effect on the permeability of water molecules and ions. By using pSLN and T18A, our study provides helpful information on the pore-forming mechanism of SLN and furthers our understanding of the regulatory mechanisms underlying the permeation of ions and water molecules in the pentameric SLN channel. |
| Databáze: | OpenAIRE |
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