Structure and Function of FS50, a salivary protein from the flea Xenopsylla cheopis that blocks the sodium channel NaV1.5.
文献类型：期刊论文
| 作者 | Xu XQ[*]1,2; Zhang B1; Andersen JF[*]2; Yang SL3; An S3; Ribeiro JM2 |
| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2016 |
| 卷号 | 6期号:X页码:e36574 |
| 通讯作者 | xu2003@smu.edu.cn |
| 合作状况 | 其它 |
| 英文摘要 | Naturally occurring toxins have been invaluable tools for the study of structural and functional relationships of voltage-gated sodium channels (VGSC). Few studies have been made of potential channel-modulating substances from blood-feeding arthropods. He we describe the characterization FS50, a salivary protein from the flea, Xenopsylla cheopis, that exhibits an inhibitory activity against the NaV1.5 channel with an IC50 of 1.58 μM. The pore-blocking mechanism of this toxin is evident from the kinetics of activation and inactivation suggesting that FS50 does not interfere with the voltage sensor of NaV1.5. FS50 exhibits high specificity for NaV1.5, since 10 μM FS50 had no discernable effect on voltage-gated Na+, K+ and Ca2+ channels in rat dorsal root ganglia or VGSC forms individually expressed in HEK 293T cells. Furthermore, intravenous injection of FS50 into rats and monkeys elicited recovery from arrhythmia induced by BaCl2, as would be expected from a blockade of NaV1.5. The crystal structure of FS50 revealed a βαββ domain similar to that of scorpion β toxin and a small N-terminal βαβ domain. Site-directed mutagenesis experiments have implicated a basic surface including the side chains of Arg 6, His 11 and Lys 32 as potentially important in the FS50 NaV1.5 interaction. |
| 收录类别 | SCI |
| 资助信息 | This work was supported in part by the Chinese National Natural Science Foundation (3137078), the Chinese Ministry of Science and Technology (2010CB529800) and the National Institutes of Health intramural research program of NIAID. |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/10631]  |
| 专题 | 昆明动物研究所_动物毒素室 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China 2.The Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20852 USA 3.The Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China |
| 推荐引用方式 GB/T 7714 | Xu XQ[*],Zhang B,Andersen JF[*],et al. Structure and Function of FS50, a salivary protein from the flea Xenopsylla cheopis that blocks the sodium channel NaV1.5.[J]. SCIENTIFIC REPORTS,2016,6(X):e36574. |
| APA | Xu XQ[*],Zhang B,Andersen JF[*],Yang SL,An S,&Ribeiro JM.(2016).Structure and Function of FS50, a salivary protein from the flea Xenopsylla cheopis that blocks the sodium channel NaV1.5..SCIENTIFIC REPORTS,6(X),e36574. |
| MLA | Xu XQ[*],et al."Structure and Function of FS50, a salivary protein from the flea Xenopsylla cheopis that blocks the sodium channel NaV1.5.".SCIENTIFIC REPORTS 6.X(2016):e36574. |
入库方式： OAI收割
来源：昆明动物研究所
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