Cryo-EM structure of the human chemerin receptor 1-Gi protein complex bound to the C-terminal nonapeptide of chemerin
文献类型：期刊论文
| 作者 | Wang, Junlin2; Chen, Geng2; Liao, Qiwen2; Lyu, Wenping1; Liu, Aijun; Zhu, Lizhe2; Du, Yang2; Ye, Richard D.2 |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2023-03-14 |
| 卷号 | 120期号:11页码:8 |
| 关键词 | GPCRs chemerin adipokine innate immunity cryo-EM |
| ISSN号 | 0027-8424 |
| DOI | 10.1073/pnas.2214324120 |
| 通讯作者 | Du, Yang(yangdu@cuhk.edu.cn) ; Ye, Richard D.(richardye@cuhk.edu.cn) |
| 英文摘要 | Chemerin is a processed protein that acts on G protein-coupled receptors (GPCRs) for its chemotactic and adipokine activities. The biologically active chemerin (chemerin 21-157) results from proteolytic cleavage of prochemerin and uses its C-terminal peptide containing the sequence YFPGQFAFS for receptor activation. Here we report a high-resolution cryo-electron microscopy (cryo-EM) structure of human chemerin receptor 1 (CMKLR1) bound to the C-terminal nonapeptide of chemokine (C9) in complex with Gi proteins. C9 inserts its C terminus into the binding pocket and is stabilized through hydrophobic interactions involving its Y1, F2, F6, and F8, as well as polar interactions between G4, S9, and several amino acids lining the binding pocket of CMKLR1. Microsecond scale molecular dynamics simulations support a balanced force distribution across the whole ligand-receptor interface that enhances thermodynamic stability of the captured binding pose of C9. The C9 interaction with CMKLR1 is drastically different from chemokine recognition by chemokine receptors, which follow a two-site two-step model. In contrast, C9 takes an "S"-shaped pose in the binding pocket of CMKLR1 much like angiotensin II in the AT1 receptor. Our mutagenesis and functional analyses confirmed the cryo-EM structure and key residues in the binding pocket for these interactions. Our findings provide a structural basis for chemerin recognition by CMKLR1 for the established chemotactic and adipokine activities. |
| WOS关键词 | INTERNATIONAL UNION ; DENDRITIC CELLS ; INFLAMMATION ; NOMENCLATURE ; MACROPHAGES ; EXPRESSION ; ADIPOKINE ; ANALOGS ; OBESITY ; CHEMR23 |
| 资助项目 | Shenzhen Natural Science Foundation ; Shenzhen Science and Technology Program[GXWD20201231105722002-20200831175432002] ; Guangdong Basic and Applied Basic Research Foundation[JCYJ20200109150019113] ; Guangdong Basic and Applied Basic Research Foundation[2020A1515110726] ; National Natural Science Foundation of China[2020A1515111173] ; National Natural Science Foundation of China[82104183] ; Ganghong Young Scholar Development Fund ; Fellowship of China Postdoctoral Science Foundation[32070950] ; Presidential Fellowship of The Chinese University of Hong Kong, Shenzhen ; Kobilka Institute of Innovative Drug Discovery at The Chinese University of Hong Kong, Shenzhen ; [2021M703092] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001169165900003 |
| 出版者 | NATL ACAD SCIENCES |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309907]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Du, Yang; Ye, Richard D. |
| 作者单位 | 1.Chinese Univ Hong Kong, Kobilka Inst Innovat Drug Discovery, Sch Med, Shenzhen 518172, Guangdong, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Junlin,Chen, Geng,Liao, Qiwen,et al. Cryo-EM structure of the human chemerin receptor 1-Gi protein complex bound to the C-terminal nonapeptide of chemerin[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2023,120(11):8. |
| APA | Wang, Junlin.,Chen, Geng.,Liao, Qiwen.,Lyu, Wenping.,Liu, Aijun.,...&Ye, Richard D..(2023).Cryo-EM structure of the human chemerin receptor 1-Gi protein complex bound to the C-terminal nonapeptide of chemerin.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,120(11),8. |
| MLA | Wang, Junlin,et al."Cryo-EM structure of the human chemerin receptor 1-Gi protein complex bound to the C-terminal nonapeptide of chemerin".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 120.11(2023):8. |
入库方式： OAI收割
来源：上海药物研究所
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