Structural basis for auxiliary subunit KCTD16 regulation of the GABA(B) receptor
文献类型：期刊论文
| 作者 | Zuo, Hao2; Glaaser, Ian2,3; Zhao, Yulin3; Kurinov, Igor1; Mosyak, Lidia2; Wang, Haonan4,5; Liu, Jonathan2; Park, Jinseo2; Frangaj, Aurel2; Sturchler, Emmanuel6 |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2019-04-23 |
| 卷号 | 116期号:17页码:8370-8379 |
| 关键词 | GABA(B) receptor KCTD Principal and auxiliary subunits crystal structure |
| ISSN号 | 0027-8424 |
| DOI | 10.1073/pnas.1903024116 |
| 通讯作者 | Geng, Yong(gengyong@simm.ac.cn) ; Slesinger, Paul A.(paul.slesinger@mssm.edu) ; Fan, Qing R.(qf13@cumc.columbia.edu) |
| 英文摘要 | Metabotropic GABA(B) receptors mediate a significant fraction of inhibitory neurotransmission in the brain. Native GABA(B) receptor complexes contain the principal subunits GABA(B1) and GABA(B2), which form an obligate heterodimer, and auxiliary subunits, known as potassium channel tetramerization domain-containing proteins (KCTDs). KCTDs interact with GABA(B) receptors and modify the kinetics of GABA(B )receptor signaling. Little is known about the molecular mechanism governing the direct association and functional coupling of GABA(B) receptors with these auxiliary proteins. Here, we describe the high-resolution structure of the KCTD16 oligomerization domain in complex with part of the GABA(B2) receptor. A single GABA(B2) Cterminal peptide is bound to the interior of an open pentamer formed by the oligomerization domain of five KCTD16 subunits. Mutation of specific amino acids identified in the structure of theGABA(B2)-KCTD16 interface disrupted both the biochemical association and functional modulation of GABA(B) receptors and G protein-activated inwardly rectifying K(+)channel (GIRK) channels. These interfacial residues are conserved among KCTDs, suggesting a common mode of KCTD interaction with GABA(B) receptors. Defining the binding interface of GABA(B) receptor and KCTD reveals a potential regulatory site for modulating GABA(B)-receptor function in the brain. |
| WOS关键词 | AMINOBUTYRIC ACID(B) RECEPTORS ; TETRAMERIZATION DOMAIN ; CRYSTAL-STRUCTURE ; GB2 SUBUNITS ; ACTIVATION ; FAMILY ; IDENTIFICATION ; EXPRESSION ; MECHANISM ; INSIGHTS |
| 资助项目 | NIH[P41 GM103403] ; NIH[S10 RR029205] ; NIH[R01GM088454] ; NIH[R01GM125801] ; NIH[R01DA037170] ; NIH[R01AA018734] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000465363700047 |
| 出版者 | NATL ACAD SCIENCES |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/289998]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Geng, Yong; Slesinger, Paul A.; Fan, Qing R. |
| 作者单位 | 1.Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA 2.Columbia Univ, Dept Pharmacol, New York, NY 10032 USA 3.Icahn Sch Med Mt Sinai, Friedman Brain Inst, Friedman Brain Inst, Nash Family Dept Neurosci, New York, NY 10029 USA 4.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Struct & Funct Drug Targets, Key Lab Receptor Res, Shanghai 201203, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Scripps Translat Sci Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA 7.Baylor Coll Med, Verma & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA 8.Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA |
| 推荐引用方式 GB/T 7714 | Zuo, Hao,Glaaser, Ian,Zhao, Yulin,et al. Structural basis for auxiliary subunit KCTD16 regulation of the GABA(B) receptor[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2019,116(17):8370-8379. |
| APA | Zuo, Hao.,Glaaser, Ian.,Zhao, Yulin.,Kurinov, Igor.,Mosyak, Lidia.,...&Fan, Qing R..(2019).Structural basis for auxiliary subunit KCTD16 regulation of the GABA(B) receptor.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,116(17),8370-8379. |
| MLA | Zuo, Hao,et al."Structural basis for auxiliary subunit KCTD16 regulation of the GABA(B) receptor".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 116.17(2019):8370-8379. |
入库方式： OAI收割
来源：上海药物研究所
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