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DOI | 10.1126/science.aar7389 |
Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation | |
Kim, Youngjin; Chen, Jue | |
2018-02-23 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 359期号:6378页码:915-919 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | The multidrug transporter permeability (P)-glycoprotein is an adenosine triphosphate (ATP)-binding cassette exporter responsible for clinical resistance to chemotherapy. P-glycoprotein extrudes toxic molecules and drugs from cells through ATP-powered conformational changes. Despite decades of effort, only the structures of the inward-facing conformation of P-glycoprotein are available. Here we present the structure of human P-glycoprotein in the outward-facing conformation, determined by cryo-electron microscopy at 3.4-angstrom resolution. The two nucleotide-binding domains form a closed dimer occluding two ATP molecules. The drug-binding cavity observed in the inward-facing structures is reorientated toward the extracellular space and compressed to preclude substrate binding. This observation indicates that ATP binding, not hydrolysis, promotes substrate release. The structure evokes a model in which the dynamic nature of P-glycoprotein enables translocation of a large variety of substrates. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000425752600045 |
WOS关键词 | NUCLEOTIDE-BINDING DOMAINS ; MULTIDRUG-RESISTANCE ; CATALYTIC CYCLE ; DRUG-BINDING ; MEMBRANE GLYCOPROTEIN ; GLUTAMATE RESIDUES ; ALTERNATING ACCESS ; ABC TRANSPORTERS ; CELLS ; HYDROLYSIS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
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文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/198033 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | Rockefeller Univ, Howard Hughes Med Inst, 1230 York Ave, New York, NY 10065 USA |
推荐引用方式 GB/T 7714 | Kim, Youngjin,Chen, Jue. Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation[J]. SCIENCE,2018,359(6378):915-919. |
APA | Kim, Youngjin,&Chen, Jue.(2018).Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation.SCIENCE,359(6378),915-919. |
MLA | Kim, Youngjin,et al."Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation".SCIENCE 359.6378(2018):915-919. |
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