☆ 4.5 Article

Crystal structure of the human angiotensin II type 2 receptor bound to an angiotensin II analog

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2018)

获取全文
添加到收藏夹

期刊

NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 25, 期 7, 页码 570-+

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/s41594-018-0079-8

关键词

-

类别

Biochemistry & Molecular Biology Biophysics Cell Biology

资金

  1. Japan Society for the Promotion of Science (JSPS) [15J04343, 22590270]
  2. JSPS postdoctoral fellowship
  3. Platform Project for Supporting Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics and Structural Life Science)
  4. Basis for Supporting Innovative Drug Discovery and Life Science Research from the Japan Agency for Medical Research and Development (AMED)
  5. JST/PRESTO
  6. Takeda Science Foundation
  7. Grants-in-Aid for Scientific Research [15J04343, 22590270] Funding Source: KAKEN

向作者/读者索取更多资源

Protocol

社区支持

Reagent

社区支持

Angiotensin II (AngII) plays a central role in regulating human blood pressure, which is mainly mediated by interactions between AngII and the G-protein-coupled receptors (GPCRs) AngII type 1 receptor (AT(1)R) and AngII type 2 receptor (AT(2)R). We have solved the crystal structure of human AT2R binding the peptide ligand [Sar(1), Ile(8)] AngII and its specific antibody at 3.2-angstrom resolution. [Sar(1), Ile(8)] AngII interacts with both the 'core' binding domain, where the small-molecule ligands of AT(1)R and AT(2)R bind, and the 'extended' binding domain, which is equivalent to the allosteric modulator binding site of muscarinic acetylcholine receptor. We generated an antibody fragment to stabilize the extended binding domain that functions as a positive allosteric modulator. We also identified a signature positively charged cluster, which is conserved among peptide-binding receptors, to locate C termini at the bottom of the binding pocket. The reported results should help with designing ligands for angiotensin receptors and possibly to other peptide GPCRs.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Biochemistry & Molecular Biology

The Crystal Structure of Angiotensin II Type 2 Receptor with Endogenous Peptide Hormone

Hidetsugu Asada, Asuka Inoue, Francois Marie Ngako Kadji, Kunio Hirata, Yuki Shiimura, Dohyun Im, Tatsuro Shimamura, Norimichi Nomura, Hiroko Iwanari, Takao Hamakubo, Osamu Kusano-Arai, Hiromi Hisano, Tomoko Uemura, Chiyo Suno, Junken Aoki, So Iwata

STRUCTURE (2020)

添加到收藏夹
Article Multidisciplinary Sciences

The discovery of a new antibody for BRIL-fused GPCR structure determination

Hikaru Miyagi, Hidetsugu Asada, Michihiko Suzuki, Yuichi Takahashi, Mai Yasunaga, Chiyo Suno, So Iwata, Jun-ichi Saito

SCIENTIFIC REPORTS (2020)

添加到收藏夹
Article Cell Biology

Binding pathway determines norepinephrine selectivity for the human β1AR over β2AR

Xinyu Xu, Jonas Kaindl, Mary J. Clark, Harald Hubner, Kunio Hirata, Roger K. Sunahara, Peter Gmeiner, Brian K. Kobilka, Xiangyu Liu

Summary: Beta adrenergic receptors mediate physiological responses to catecholamines epinephrine and norepinephrine, and norepinephrine shows higher affinity for beta(1)AR. Crystal structure analysis revealed identical catecholamine-binding pockets but differences in extracellular vestibules between beta(1)AR and beta(2)AR, influencing norepinephrine binding path and affinity.

CELL RESEARCH (2021)

添加到收藏夹
Article Multidisciplinary Sciences

An unprecedented insight into the catalytic mechanism of copper nitrite reductase from atomic-resolution and damage-free structures

Samuel L. Rose, Svetlana Antonyuk, Daisuke Sasaki, Keitaro Yamashita, Kunio Hirata, Go Ueno, Hideo Ago, Robert R. Eady, Takehiko Tosha, Masaki Yamamoto, S. Samar Hasnain

Summary: Two copies of nirK genes were identified in several rhizobia, including Bradyrhizobium sp. ORS 375, which encode a four-domain heme-CuNiR and a two-domain CuNiR. Despite a 70% sequence identity, the blue CuNiR showed substantially lower catalytic efficiency compared to other well-studied CuNiRs. Advanced synchrotron radiation and x-ray free-electron laser techniques were used to reveal the difference in catalytic efficiency among CuNiRs.

SCIENCE ADVANCES (2021)

添加到收藏夹
Article Instruments & Instrumentation

Guidelines for de novo phasing using multiple small-wedge data collection

Seiki Baba, Hiroaki Matsuura, Takashi Kawamura, Naoki Sakai, Yuki Nakamura, Yoshiaki Kawano, Nobuhiro Mizuno, Takashi Kumasaka, Masaki Yamamoto, Kunio Hirata

Summary: This study demonstrates the importance of selecting a radiation dose lower than 10 MGy for de novo structure determination using SWSX. Data collection at a dose of 5 MGy is shown to be optimal for balancing signal availability while minimizing damage.

JOURNAL OF SYNCHROTRON RADIATION (2021)

添加到收藏夹
Article Multidisciplinary Sciences

Endogenous agonist-bound S1PR3 structure reveals determinants of G protein-subtype bias

Shintaro Maeda, Yuki Shiimura, Hidetsugu Asada, Kunio Hirata, Fangjia Luo, Eriko Nango, Nobuo Tanaka, Masayasu Toyomoto, Asuka Inoue, Junken Aoki, So Iwata, Masatoshi Hagiwara

Summary: Sphingosine-1-phosphate (S1P) regulates various important physiological functions through its receptors, with the crystal structure of active human S1PR3 in complex with S1P revealing insights into its activation mechanism and G protein selectivity. These findings could aid in the development of optimized therapeutic strategies.

SCIENCE ADVANCES (2021)

添加到收藏夹
Article Biology

The structure of an archaeal oligosaccharyltransferase provides insight into the strict exclusion of proline from the N-glycosylation sequon

Yuya Taguchi, Takahiro Yamasaki, Marie Ishikawa, Yuki Kawasaki, Ryuji Yukimura, Maki Mitani, Kunio Hirata, Daisuke Kohda

Summary: The study elucidates the structural basis for the exclusion of proline residues from N-glycosylation sequons by oligosaccharyltransferase, highlighting the essential role of the TIXE motif and its adjacent regions in this process. This provides valuable insight into the sequon specificity of N-glycosylation, a major posttranslational modification in eukaryotes.

COMMUNICATIONS BIOLOGY (2021)

添加到收藏夹
Correction Instruments & Instrumentation

Guidelines for de novo phasing using multiple small-wedge data collection (vol 28, pg 1284, 2021)

Seiki Baba, Hiroaki Matsuura, Takashi Kawamura, Naoki Sakai, Yuki Nakamura, Yoshiaki Kawano, Nobuhiro Mizuno, Takashi Kumasaka, Masaki Yamamoto, Kunio Hirata

JOURNAL OF SYNCHROTRON RADIATION (2022)

添加到收藏夹
Article Biochemistry & Molecular Biology

A methodology for creating mutants of G-protein coupled receptors stabilized in active state by combining statistical thermodynamics and evolutionary molecular engineering

Taisei Yamamoto, Satoshi Yasuda, Rinshi S. Kasai, Ryosuke Nakano, Simon Hikiri, Kanna Sugaya, Tomohiko Hayashi, Satoshi Ogasawara, Mitsunori Shiroishi, Takahiro K. Fujiwara, Masahiro Kinoshita, Takeshi Murata

Summary: The study challenged the stabilization of a GPCR in the active state solely by multiple amino-acid mutations, revealing that stabilizing the inactive state leads to a significant increase in thermal denaturation midpoint temperature T-m, but this is not always the case for the active state. The methodology involving statistical thermodynamics and evolutionary molecular engineering was able to identify mutants with higher binding affinity for G protein, shifting structural characteristics towards the active state, although only slight increases in T-m were observed, indicating its unsuitability as a stability measure for the active state.

PROTEIN SCIENCE (2022)

添加到收藏夹
Article Multidisciplinary Sciences

Mechanistic insights into intramembrane proteolysis by E. coli site-2 protease homolog RseP

Yuki Imaizumi, Kazunori Takanuki, Takuya Miyake, Mizuki Takemoto, Kunio Hirata, Mika Hirose, Rika Oi, Tatsuya Kobayashi, Kenichi Miyoshi, Rie Aruga, Tatsuhiko Yokoyama, Shizuka Katagiri, Hiroaki Matsuura, Kenji Iwasaki, Takayuki Kato, Mika K. Kaneko, Yukinari Kato, Michiko Tajiri, Satoko Akashi, Osamu Nureki, Yohei Hizukuri, Yoshinori Akiyama, Terukazu Nogi

Summary: Site-2 proteases are a conserved family of intramembrane proteases that regulate signal transduction and maintain proteostasis by cleaving transmembrane substrates. The crystal structures of inhibitor-bound forms of bacterial site-2 proteases were determined, revealing that conformational changes in the RseP domains expose the substrate-binding site. Mutational analysis showed that the conformational changes are mediated by a conserved electrostatic linkage between transmembrane and peripheral membrane-associated domains. In vivo cleavage assays supported the model that the substrate transmembrane helix is unwound and clamped by the active center of RseP for efficient cleavage.

SCIENCE ADVANCES (2022)

添加到收藏夹
Article Multidisciplinary Sciences

Genome destabilization-associated phenotypes arising as a consequence of therapeutic treatment are suppressed by Olaparib

Mafuka Suzuki, Haruka Fujimori, Kakeru Wakatsuki, Yuya Manaka, Haruka Asai, Mai Hyodo, Yusuke Matsuno, Rika Kusumoto-Matsuo, Mitsunori Shiroishi, Ken-ichi Yoshioka

Summary: Malignancy is often accompanied by therapeutic resistance and metastasis, which typically occur after treatment. It has been found that DNA double strand breaks (DSBs) induced by camptothecin (CPT) and radiation can endanger genome stability in surviving cancer cells, leading to the development of resistance. Accumulation of cytosolic DNA due to genomic destabilization activates the cGAS/STING pathway, ultimately resulting in increased cell migration and metastasis. Interestingly, the PARP inhibitor Olaparib can suppress these genomic destabilization-associated phenotypes, reducing the risk of therapeutic resistance and cell migration.

PLOS ONE (2023)

添加到收藏夹
Article Biochemistry & Molecular Biology

Molecular basis for anti-insomnia drug design from structure of lemborexant-bound orexin 2 receptor

Hidetsugu Asada, Dohyun Im, Yunhon Hotta, Satoshi Yasuda, Takeshi Murata, Ryoji Suno, So Iwata

Summary: The study uncovers the importance of orexin receptors in regulating the sleep-wake cycle and highlights the potential of developing antagonists for these receptors as novel treatments for sleep-related diseases. The determination of the structure of OX2R bound to lemborexant provides valuable insights into the binding mechanism and furthers our understanding of the pharmacophore models and target selectivity to OXRs.

STRUCTURE (2022)

添加到收藏夹
Article Biochemical Research Methods

Elucidating polymorphs of crystal structures by intensity-based hierarchical clustering analysis of multiple diffraction data sets

Hiroaki Matsuura, Naoki Sakai, Sachiko Toma-Fukai, Norifumi Muraki, Koki Hayama, Hironari Kamikubo, Shigetoshi Aono, Yoshiaki Kawano, Masaki Yamamoto, Kunio Hirata

Summary: In macromolecular structure determination using X-ray diffraction from multiple crystals, hierarchical clustering analysis (HCA) has been effective in classifying polymorphous data sets with a certain threshold, allowing for the identification of polymorphs in data sets with unknown structural heterogeneity. Additionally, polymorphs can also be detected in single crystals using the continuous helical scheme.

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY (2023)

添加到收藏夹
暂无数据
研讨会 海报 问题 讨论圈 基金 期刊 论文 科研社交 资讯集成 审稿人 关于我们 常见问题 移动App 隐私条款 使用条款
© Peeref 2019-2024. All rights reserved.