Structure of CC Chemokine Receptor 5 with a Potent Chemokine Antagonist RevealsMechanisms of Chemokine Recognition and Molecular Mimicry by HIV
文献类型：期刊论文
| 作者 | Zheng, Yi1; Han, Gye Won4; Abagyan, Ruben1; Wu, Beili3 ; Stevens, Raymond C.2,5; Cherezov, Vadim4; Kufareva, Irina1; Handel, Tracy M.1
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| 刊名 | IMMUNITY
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| 出版日期 | 2017-06-20 |
| 卷号 | 46期号:6页码:1005-+ |
| ISSN号 | 1074-7613 |
| DOI | 10.1016/j.immuni.2017.05.002 |
| 文献子类 | Article |
| 英文摘要 | CCR5 is the primary chemokine receptor utilized by HIV to infect leukocytes, whereas CCR5 ligands inhibit infection by blocking CCR5 engagement with HIV gp120. To guide the design of improved therapeutics, we solved the structure of CCR5 in complex with chemokine antagonist [5P7]CCL5. Several structural features appeared to contribute to the anti-HIV potency of [5P7]CCL5, including the distinct chemokine orientation relative to the receptor, the near-complete occupancy of the receptor binding pocket, the dense network of intermolecular hydrogen bonds, and the similarity of binding determinants with the FDA-approved HIV inhibitor Maraviroc. Molecular modeling indicated that HIV gp120 mimicked the chemokine interaction with CCR5, providing an explanation for the ability of CCR5 to recognize diverse ligands and gp120 variants. Our findings reveal that structural plasticity facilitates receptor- chemokine specificity and enables exploitation by HIV, and provide insight into the design of small molecule and protein inhibitors for HIV and other CCR5-mediated diseases. |
| WOS关键词 | IMMUNODEFICIENCY-VIRUS TYPE-1 ; AMINO-TERMINAL DOMAIN ; HIGH-AFFINITY BINDING ; MEMBRANE-PROTEINS ; CRYSTAL-STRUCTURE ; N-TERMINUS ; RANTES ; CORECEPTOR ; ENTRY ; GP120 |
| 资助项目 | National Institutes of Health[R01 AI118985] ; National Institutes of Health[R01 GM117424] ; National Institutes of Health[R21 AI121918] ; National Institutes of Health[R21 AI122211] ; National Institutes of Health[R01 GM071872] ; National Cancer Institute[ACB-12002] ; National Institute of General Medical Sciences[AGM-12006] ; US Department of Energy (DOE) Office of Science[DE-AC02-06CH11357] |
| WOS研究方向 | Immunology |
| 语种 | 英语 |
| 出版者 | CELL PRESS |
| WOS记录号 | WOS:000403665900014 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272599]  |
| 专题 | 药物靶标结构与功能中心 |
| 通讯作者 | Kufareva, Irina; Handel, Tracy M. |
| 作者单位 | 1.Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA; 2.Univ Southern Calif, Bridge Inst, Dept Biol Sci, Los Angeles, CA 90089 USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 4.Univ Southern Calif, Bridge Inst, Dept Chem, Los Angeles, CA 90089 USA; 5.Univ Southern Calif, Bridge Inst, Dept Chem, Los Angeles, CA 90089 USA |
| 推荐引用方式 GB/T 7714 | Zheng, Yi,Han, Gye Won,Abagyan, Ruben,et al. Structure of CC Chemokine Receptor 5 with a Potent Chemokine Antagonist RevealsMechanisms of Chemokine Recognition and Molecular Mimicry by HIV[J]. IMMUNITY,2017,46(6):1005-+. |
| APA | Zheng, Yi.,Han, Gye Won.,Abagyan, Ruben.,Wu, Beili.,Stevens, Raymond C..,...&Handel, Tracy M..(2017).Structure of CC Chemokine Receptor 5 with a Potent Chemokine Antagonist RevealsMechanisms of Chemokine Recognition and Molecular Mimicry by HIV.IMMUNITY,46(6),1005-+. |
| MLA | Zheng, Yi,et al."Structure of CC Chemokine Receptor 5 with a Potent Chemokine Antagonist RevealsMechanisms of Chemokine Recognition and Molecular Mimicry by HIV".IMMUNITY 46.6(2017):1005-+. |
入库方式： OAI收割
来源：上海药物研究所
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