Structural Analyses of Toll-like Receptor 7 Reveal Detailed RNA Sequence Specificity and Recognition Mechanism of Agonistic Ligands

Zhikuan Zhang; Umeharu Ohto; Takuma Shibata; Masato Taoka; Yoshio Yamauchi; Ryota Sato; Nikunj M. Shukla; Sunil A. David; Toshiaki Isobe; Kensuke Miyake; Toshiyuki Shimizu

doi:10.1016/j.celrep.2018.11.081

Structural Analyses of Toll-like Receptor 7 Reveal Detailed RNA Sequence Specificity and Recognition Mechanism of Agonistic Ligands

Zhikuan Zhang, Umeharu Ohto, Takuma Shibata, Masato Taoka, Yoshio Yamauchi, Ryota Sato, Nikunj M. Shukla, Sunil A. David, Toshiaki Isobe, Kensuke Miyake, Toshiyuki Shimizu

Medicinal Chemistry

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67 Scopus citations

Abstract

Zhang et al. determine a series of crystal structures of TLR7 complexed with agonistic ligands. The findings contain detailed ssRNA sequence specificity, recognition mechanism(s) of synthetic ligands, the molecular basis of TLR7 and TLR8 ligand selectivity, and identification of possible endogenous ligands with a high activity.

Original language	English (US)
Pages (from-to)	3371-3381.e5
Journal	Cell reports
Volume	25
Issue number	12
DOIs	https://doi.org/10.1016/j.celrep.2018.11.081
State	Published - Dec 18 2018

Bibliographical note

Funding Information:
We thank the Beamline staff members at Photon Factory and SPring-8 for their assistance with data collection. Especially, we thank Y. Yamada and A. Shinoda for automated data collection at Photon Factory and K. Hirata for data collection at SPring-8 BL32XU. This work was supported by the Japanese Ministry of Education, Culture, Sports, Science, and Technology (grants 26711002 to U.O., 16K08827 to T. Shibata, 16H06388 to K.M., and 16H02494 to T. Shimizu), CREST-JST (to T. Shibata and T. Shimizu), the Takeda Science Foundation (to U.O. and T. Shimizu), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to U.O.), the Daiichi Sankyo Foundation of Life Science (to U.O.), the Uehara Memorial Foundation (to T. Shimizu), and the Naito Foundation (to U.O. and T. Shimizu). S.A.D. and N.M.S. gratefully acknowledge NIH/NIAID contracts HSN272200900033C and HHSN272201400056C . This research is partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) from the Japan Agency for Medical Research and Development (AMED) under grant JP18am0101070 .

Funding Information:
We thank the Beamline staff members at Photon Factory and SPring-8 for their assistance with data collection. Especially, we thank Y. Yamada and A. Shinoda for automated data collection at Photon Factory and K. Hirata for data collection at SPring-8 BL32XU. This work was supported by the Japanese Ministry of Education, Culture, Sports, Science, and Technology (grants 26711002 to U.O., 16K08827 to T. Shibata, 16H06388 to K.M., and 16H02494 to T. Shimizu), CREST-JST (to T. Shibata and T. Shimizu), the Takeda Science Foundation (to U.O. and T. Shimizu), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to U.O.), the Daiichi Sankyo Foundation of Life Science (to U.O.), the Uehara Memorial Foundation (to T. Shimizu), and the Naito Foundation (to U.O. and T. Shimizu). S.A.D. and N.M.S. gratefully acknowledge NIH/NIAID contracts HSN272200900033C and HHSN272201400056C. This research is partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) from the Japan Agency for Medical Research and Development (AMED) under grant JP18am0101070.

Publisher Copyright:
© 2018 The Author(s)

Keywords

Toll-like receptor
guanosine 2′,3′-cyclic phosphate
innate immunity
low-molecular-weight agonists
single-stranded RNA

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10.1016/j.celrep.2018.11.081

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title = "Structural Analyses of Toll-like Receptor 7 Reveal Detailed RNA Sequence Specificity and Recognition Mechanism of Agonistic Ligands",

abstract = "Zhang et al. determine a series of crystal structures of TLR7 complexed with agonistic ligands. The findings contain detailed ssRNA sequence specificity, recognition mechanism(s) of synthetic ligands, the molecular basis of TLR7 and TLR8 ligand selectivity, and identification of possible endogenous ligands with a high activity.",

keywords = "Toll-like receptor, guanosine 2′,3′-cyclic phosphate, innate immunity, low-molecular-weight agonists, single-stranded RNA",

author = "Zhikuan Zhang and Umeharu Ohto and Takuma Shibata and Masato Taoka and Yoshio Yamauchi and Ryota Sato and Shukla, {Nikunj M.} and David, {Sunil A.} and Toshiaki Isobe and Kensuke Miyake and Toshiyuki Shimizu",

note = "Funding Information: We thank the Beamline staff members at Photon Factory and SPring-8 for their assistance with data collection. Especially, we thank Y. Yamada and A. Shinoda for automated data collection at Photon Factory and K. Hirata for data collection at SPring-8 BL32XU. This work was supported by the Japanese Ministry of Education, Culture, Sports, Science, and Technology (grants 26711002 to U.O., 16K08827 to T. Shibata, 16H06388 to K.M., and 16H02494 to T. Shimizu), CREST-JST (to T. Shibata and T. Shimizu), the Takeda Science Foundation (to U.O. and T. Shimizu), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to U.O.), the Daiichi Sankyo Foundation of Life Science (to U.O.), the Uehara Memorial Foundation (to T. Shimizu), and the Naito Foundation (to U.O. and T. Shimizu). S.A.D. and N.M.S. gratefully acknowledge NIH/NIAID contracts HSN272200900033C and HHSN272201400056C . This research is partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) from the Japan Agency for Medical Research and Development (AMED) under grant JP18am0101070 . Funding Information: We thank the Beamline staff members at Photon Factory and SPring-8 for their assistance with data collection. Especially, we thank Y. Yamada and A. Shinoda for automated data collection at Photon Factory and K. Hirata for data collection at SPring-8 BL32XU. This work was supported by the Japanese Ministry of Education, Culture, Sports, Science, and Technology (grants 26711002 to U.O., 16K08827 to T. Shibata, 16H06388 to K.M., and 16H02494 to T. Shimizu), CREST-JST (to T. Shibata and T. Shimizu), the Takeda Science Foundation (to U.O. and T. Shimizu), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to U.O.), the Daiichi Sankyo Foundation of Life Science (to U.O.), the Uehara Memorial Foundation (to T. Shimizu), and the Naito Foundation (to U.O. and T. Shimizu). S.A.D. and N.M.S. gratefully acknowledge NIH/NIAID contracts HSN272200900033C and HHSN272201400056C. This research is partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) from the Japan Agency for Medical Research and Development (AMED) under grant JP18am0101070. Publisher Copyright: {\textcopyright} 2018 The Author(s)",

year = "2018",

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doi = "10.1016/j.celrep.2018.11.081",

language = "English (US)",

volume = "25",

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T1 - Structural Analyses of Toll-like Receptor 7 Reveal Detailed RNA Sequence Specificity and Recognition Mechanism of Agonistic Ligands

AU - Zhang, Zhikuan

AU - Ohto, Umeharu

AU - Shibata, Takuma

AU - Taoka, Masato

AU - Yamauchi, Yoshio

AU - Sato, Ryota

AU - Shukla, Nikunj M.

AU - David, Sunil A.

AU - Isobe, Toshiaki

AU - Miyake, Kensuke

AU - Shimizu, Toshiyuki

N1 - Funding Information: We thank the Beamline staff members at Photon Factory and SPring-8 for their assistance with data collection. Especially, we thank Y. Yamada and A. Shinoda for automated data collection at Photon Factory and K. Hirata for data collection at SPring-8 BL32XU. This work was supported by the Japanese Ministry of Education, Culture, Sports, Science, and Technology (grants 26711002 to U.O., 16K08827 to T. Shibata, 16H06388 to K.M., and 16H02494 to T. Shimizu), CREST-JST (to T. Shibata and T. Shimizu), the Takeda Science Foundation (to U.O. and T. Shimizu), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to U.O.), the Daiichi Sankyo Foundation of Life Science (to U.O.), the Uehara Memorial Foundation (to T. Shimizu), and the Naito Foundation (to U.O. and T. Shimizu). S.A.D. and N.M.S. gratefully acknowledge NIH/NIAID contracts HSN272200900033C and HHSN272201400056C . This research is partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) from the Japan Agency for Medical Research and Development (AMED) under grant JP18am0101070 . Funding Information: We thank the Beamline staff members at Photon Factory and SPring-8 for their assistance with data collection. Especially, we thank Y. Yamada and A. Shinoda for automated data collection at Photon Factory and K. Hirata for data collection at SPring-8 BL32XU. This work was supported by the Japanese Ministry of Education, Culture, Sports, Science, and Technology (grants 26711002 to U.O., 16K08827 to T. Shibata, 16H06388 to K.M., and 16H02494 to T. Shimizu), CREST-JST (to T. Shibata and T. Shimizu), the Takeda Science Foundation (to U.O. and T. Shimizu), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to U.O.), the Daiichi Sankyo Foundation of Life Science (to U.O.), the Uehara Memorial Foundation (to T. Shimizu), and the Naito Foundation (to U.O. and T. Shimizu). S.A.D. and N.M.S. gratefully acknowledge NIH/NIAID contracts HSN272200900033C and HHSN272201400056C. This research is partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) from the Japan Agency for Medical Research and Development (AMED) under grant JP18am0101070. Publisher Copyright: © 2018 The Author(s)

PY - 2018/12/18

Y1 - 2018/12/18

N2 - Zhang et al. determine a series of crystal structures of TLR7 complexed with agonistic ligands. The findings contain detailed ssRNA sequence specificity, recognition mechanism(s) of synthetic ligands, the molecular basis of TLR7 and TLR8 ligand selectivity, and identification of possible endogenous ligands with a high activity.

AB - Zhang et al. determine a series of crystal structures of TLR7 complexed with agonistic ligands. The findings contain detailed ssRNA sequence specificity, recognition mechanism(s) of synthetic ligands, the molecular basis of TLR7 and TLR8 ligand selectivity, and identification of possible endogenous ligands with a high activity.

KW - Toll-like receptor

KW - guanosine 2′,3′-cyclic phosphate

KW - innate immunity

KW - low-molecular-weight agonists

KW - single-stranded RNA

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DO - 10.1016/j.celrep.2018.11.081

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SN - 2211-1247

VL - 25

SP - 3371-3381.e5

JO - Cell Reports

JF - Cell Reports

IS - 12

ER -

Structural Analyses of Toll-like Receptor 7 Reveal Detailed RNA Sequence Specificity and Recognition Mechanism of Agonistic Ligands

Abstract

Bibliographical note

Keywords

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