Transverse relaxation dispersion of the p7 membrane channel from hepatitis C virus reveals conformational breathing
文献类型：期刊论文
| 作者 | Dev, J; Bruschweiler, S; Ouyang, B; Chou, JJ |
| 刊名 | JOURNAL OF BIOMOLECULAR NMR
 |
| 出版日期 | 2015 |
| 卷号 | 61期号:3页码:369-378 |
| 关键词 | Membrane protein dynamics Viroporin HCV p7 |
| 通讯作者 | Chou, JJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.,james_chou@hms.harvard.edu |
| 英文摘要 | The p7 membrane protein encoded by hepatitis C virus (HCV) assembles into a homo-hexamer that selectively conducts cations. An earlier solution NMR structure of the hexameric complex revealed a funnel-like architecture and suggests that a ring of conserved asparagines near the narrow end of the funnel are important for cation interaction. NMR based drug-binding experiments also suggest that rimantadine can allosterically inhibit ion conduction via a molecular wedge mechanism. These results suggest the presence of dilation and contraction of the funnel tip that are important for channel activity and that the action of the drug is attenuating this motion. Here, we determined the conformational dynamics and solvent accessibility of the p7 channel. The proton exchange measurements show that the cavity-lining residues are largely water accessible, consistent with the overall funnel shape of the channel. Our relaxation dispersion data show that residues Val7 and Leu8 near the asparagine ring are subject to large chemical exchange, suggesting significant intrinsic channel breathing at the tip of the funnel. Moreover, the hinge regions connecting the narrow and wide regions of the funnel show strong relaxation dispersion and these regions are the binding sites for rimantadine. Presence of rimantadine decreases the conformational dynamics near the asparagine ring and the hinge area. Our data provide direct observation of mu s-ms dynamics of the p7 channel and support the molecular wedge mechanism of rimantadine inhibition of the HCV p7 channel. |
| 学科主题 | Biochemistry & Molecular Biology; Spectroscopy |
| 类目[WOS] | Biochemistry & Molecular Biology ; Spectroscopy |
| 关键词[WOS] | WATER EXCHANGE FILTER ; ION-CHANNEL ; NMR-SPECTROSCOPY ; CHEMICAL-EXCHANGE ; CRYSTAL-STRUCTURE ; INFECTIOUS VIRUS ; PROTEIN ; MACROMOLECULES ; ARCHITECTURE ; REPLICATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000352711900017 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/32]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Dev, J,Bruschweiler, S,Ouyang, B,et al. Transverse relaxation dispersion of the p7 membrane channel from hepatitis C virus reveals conformational breathing[J]. JOURNAL OF BIOMOLECULAR NMR,2015,61(3):369-378. |
| APA | Dev, J,Bruschweiler, S,Ouyang, B,&Chou, JJ.(2015).Transverse relaxation dispersion of the p7 membrane channel from hepatitis C virus reveals conformational breathing.JOURNAL OF BIOMOLECULAR NMR,61(3),369-378. |
| MLA | Dev, J,et al."Transverse relaxation dispersion of the p7 membrane channel from hepatitis C virus reveals conformational breathing".JOURNAL OF BIOMOLECULAR NMR 61.3(2015):369-378. |
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