The structural basis for receptor recognition of human interleukin-18

Naotaka Tsutsumi; Takeshi Kimura; Kyohei Arita; Mariko Ariyoshi; Hidenori Ohnishi; Takahiro Yamamoto; Xiaobing Zuo; Katsumi Maenaka; Enoch Y. Park; Naomi Kondo; Masahiro Shirakawa; Hidehito Tochio; Zenichiro Kato

doi:10.1038/ncomms6340

The structural basis for receptor recognition of human interleukin-18

Naotaka Tsutsumi, Takeshi Kimura, Kyohei Arita, Mariko Ariyoshi, Hidenori Ohnishi, Takahiro Yamamoto, Xiaobing Zuo, Katsumi Maenaka, Enoch Y. Park, Naomi Kondo, Masahiro Shirakawa, Hidehito Tochio, Zenichiro Kato

Research output: Contribution to journal › Article › peer-review

74 Citations (Scopus)

Abstract

Interleukin (IL)-18 is a proinflammatory cytokine that belongs to the IL-1 family and plays an important role in inflammation. The uncontrolled release of this cytokine is associated with severe chronic inflammatory disease. IL-18 forms a signalling complex with the IL-18 receptor α (Rα) and β (Rβ) chains at the plasma membrane, which induces multiple inflammatory cytokines. Here, we present a crystal structure of human IL-18 bound to the two receptor extracellular domains. Generally, the receptors' recognition mode for IL-18 is similar to IL-1β; however, certain notable differences were observed. The architecture of the IL-18 receptor second domain (D2) is unique among the other IL-1R family members, which presumably distinguishes them from the IL-1 receptors that exhibit a more promiscuous ligand recognition mode. The structures and associated biochemical and cellular data should aid in developing novel drugs to neutralize IL-18 activity.

Original language	English
Article number	5340
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6340
Publication status	Published - 2014
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms6340

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@article{324cdb2b02e647ed93fa14823786f4d4,

title = "The structural basis for receptor recognition of human interleukin-18",

abstract = "Interleukin (IL)-18 is a proinflammatory cytokine that belongs to the IL-1 family and plays an important role in inflammation. The uncontrolled release of this cytokine is associated with severe chronic inflammatory disease. IL-18 forms a signalling complex with the IL-18 receptor α (Rα) and β (Rβ) chains at the plasma membrane, which induces multiple inflammatory cytokines. Here, we present a crystal structure of human IL-18 bound to the two receptor extracellular domains. Generally, the receptors' recognition mode for IL-18 is similar to IL-1β; however, certain notable differences were observed. The architecture of the IL-18 receptor second domain (D2) is unique among the other IL-1R family members, which presumably distinguishes them from the IL-1 receptors that exhibit a more promiscuous ligand recognition mode. The structures and associated biochemical and cellular data should aid in developing novel drugs to neutralize IL-18 activity.",

author = "Naotaka Tsutsumi and Takeshi Kimura and Kyohei Arita and Mariko Ariyoshi and Hidenori Ohnishi and Takahiro Yamamoto and Xiaobing Zuo and Katsumi Maenaka and Park, {Enoch Y.} and Naomi Kondo and Masahiro Shirakawa and Hidehito Tochio and Zenichiro Kato",

note = "Funding Information: X-ray data collection was supported by SPring-8 (Harima, Japan), Photon Factory (Tsukuba, Japan), Argonne National Laboratory (Illinois, USA, supported by DE-AC02-06CH11357) and Platform for Drug Discovery, Informatics, and Structural Life Science (Japan). We thank T. Tsunaka (Kyoto University) for the use of his beam time of BL44XU at SPring-8. We also thank T. Fukao, N. Kawamoto, K. Tsuji, M. Yamamoto, S. Ninomiya, T. Yano and K. Kasahara (Gifu University) for their scientific advice or technical help. Affymetrix, Inc. provided discontinued detergents to us. SAXS graphics were prepared using the UCSF Chimera package, which developed by the group at the University of California. (San Francisco, USA, supported by NIGMS P41-GM103311). This work was supported by JSPS KAKENHI Grant Number 22370038 to H.T., Grant-in-Aid for JSPS Fellows to N.T., Health and Labour Science Research Grants for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare to H.O., Health and Labour Science Research Grants for Research from the Ministry of Health, Labour and Welfare to Z.K., Science Research Grant from Eishukai to Z.K, and MEXT KAKENHI Grant Number 21790979 to T.K. Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited. All rights reserved.",

year = "2014",

doi = "10.1038/ncomms6340",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

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T1 - The structural basis for receptor recognition of human interleukin-18

AU - Tsutsumi, Naotaka

AU - Kimura, Takeshi

AU - Arita, Kyohei

AU - Ariyoshi, Mariko

AU - Ohnishi, Hidenori

AU - Yamamoto, Takahiro

AU - Zuo, Xiaobing

AU - Maenaka, Katsumi

AU - Park, Enoch Y.

AU - Kondo, Naomi

AU - Shirakawa, Masahiro

AU - Tochio, Hidehito

AU - Kato, Zenichiro

N1 - Funding Information: X-ray data collection was supported by SPring-8 (Harima, Japan), Photon Factory (Tsukuba, Japan), Argonne National Laboratory (Illinois, USA, supported by DE-AC02-06CH11357) and Platform for Drug Discovery, Informatics, and Structural Life Science (Japan). We thank T. Tsunaka (Kyoto University) for the use of his beam time of BL44XU at SPring-8. We also thank T. Fukao, N. Kawamoto, K. Tsuji, M. Yamamoto, S. Ninomiya, T. Yano and K. Kasahara (Gifu University) for their scientific advice or technical help. Affymetrix, Inc. provided discontinued detergents to us. SAXS graphics were prepared using the UCSF Chimera package, which developed by the group at the University of California. (San Francisco, USA, supported by NIGMS P41-GM103311). This work was supported by JSPS KAKENHI Grant Number 22370038 to H.T., Grant-in-Aid for JSPS Fellows to N.T., Health and Labour Science Research Grants for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare to H.O., Health and Labour Science Research Grants for Research from the Ministry of Health, Labour and Welfare to Z.K., Science Research Grant from Eishukai to Z.K, and MEXT KAKENHI Grant Number 21790979 to T.K. Publisher Copyright: © 2014 Macmillan Publishers Limited. All rights reserved.

PY - 2014

Y1 - 2014

N2 - Interleukin (IL)-18 is a proinflammatory cytokine that belongs to the IL-1 family and plays an important role in inflammation. The uncontrolled release of this cytokine is associated with severe chronic inflammatory disease. IL-18 forms a signalling complex with the IL-18 receptor α (Rα) and β (Rβ) chains at the plasma membrane, which induces multiple inflammatory cytokines. Here, we present a crystal structure of human IL-18 bound to the two receptor extracellular domains. Generally, the receptors' recognition mode for IL-18 is similar to IL-1β; however, certain notable differences were observed. The architecture of the IL-18 receptor second domain (D2) is unique among the other IL-1R family members, which presumably distinguishes them from the IL-1 receptors that exhibit a more promiscuous ligand recognition mode. The structures and associated biochemical and cellular data should aid in developing novel drugs to neutralize IL-18 activity.

AB - Interleukin (IL)-18 is a proinflammatory cytokine that belongs to the IL-1 family and plays an important role in inflammation. The uncontrolled release of this cytokine is associated with severe chronic inflammatory disease. IL-18 forms a signalling complex with the IL-18 receptor α (Rα) and β (Rβ) chains at the plasma membrane, which induces multiple inflammatory cytokines. Here, we present a crystal structure of human IL-18 bound to the two receptor extracellular domains. Generally, the receptors' recognition mode for IL-18 is similar to IL-1β; however, certain notable differences were observed. The architecture of the IL-18 receptor second domain (D2) is unique among the other IL-1R family members, which presumably distinguishes them from the IL-1 receptors that exhibit a more promiscuous ligand recognition mode. The structures and associated biochemical and cellular data should aid in developing novel drugs to neutralize IL-18 activity.

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VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 5340

ER -

The structural basis for receptor recognition of human interleukin-18

Abstract

ASJC Scopus subject areas

UN SDGs

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