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2. COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study)

Author

Arashiro, Takeshi, Miwa, Maki, Nakagawa, Hidenori, Takamatsu, Junpei, Oba, Kunihiro, Fujimi, Satoshi, Kikuchi, Hitoshi, Iwasawa, Takamasa, Kanbe, Fumiko, Oyama, Keisuke, Kanai, Masayuki, Ogata, Yoshitaka, Asakura, Takanori, Asami, Takahiro, Mizuno, Keiko, Sugita, Manabu, Jinta, Torahiko, Nishida, Yusuke, Kato, Hideaki, Atagi, Kazuaki, Higaki, Taiki, Nakano, Yoshio, Tsutsumi, Takeya, Doi, Kent, Okugawa, Shu, Ueda, Akihiro, Nakamura, Akira, Yoshida, Toru, Shimada-Sammori, Kaoru, Shimizu, Keiki, Fujita, Yasuo, Okochi, Yasumi, Tochitani, Kentaro, Nakanishi, Asuka, Rinka, Hiroshi, Taniyama, Daisuke, Yamaguchi, Asase, Uchikura, Toshio, Matsunaga, Maiko, Aono, Hiromi, Hamaguchi, Masanari, Motoda, Kentaro, Nakayama, Sohei, Yamamoto, Kei, Oka, Hideaki, Tanaka, Katsushi, Inoue, Takeshi, Kobayashi, Mieko, Fujitani, Shigeki, Tsukahara, Maki, Takeda, Saki, Stucky, Ashley, Suzuki, Tadaki, Smith, Chris, Hibberd, Martin, Ariyoshi, Koya, Fujino, Yuji, Arima, Yuzo, Takeda, Shinhiro, Hashimoto, Satoru, and Suzuki, Motoi

Published
2024
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4. Blunted humoral immune response to the fourth dose of BNT162b2 COVID-19 vaccine in patients undergoing hemodialysis

Author

Kanai, Daisuke, Wakui, Hiromichi, Hanaoka, Masaaki, Haze, Tatsuya, Azushima, Kengo, Shinoda, Satoru, Tsukamoto, Shunichiro, Taguchi, Shinya, Kinguchi, Sho, Kanaoka, Tomohiko, Toya, Yoshiyuki, Hirawa, Nobuhito, Kato, Hideaki, Watanabe, Fumimasa, Hanaoka, Kanako, Mitsuhashi, Hiroshi, Yamaguchi, Satoshi, Ohnishi, Toshimasa, and Tamura, Kouichi

Published
2023
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5. Immune escape and waning immunity of COVID-19 monovalent mRNA vaccines against symptomatic infection with BA.1/BA.2 and BA.5 in Japan

Author

Arashiro, Takeshi, Arima, Yuzo, Kuramochi, Jin, Muraoka, Hirokazu, Sato, Akihiro, Chubachi, Kumi, Oba, Kunihiro, Yanai, Atsushi, Arioka, Hiroko, Uehara, Yuki, Ihara, Genei, Kato, Yasuyuki, Yanagisawa, Naoki, Nagura, Yoshito, Yanai, Hideki, Ueda, Akihiro, Numata, Akira, Kato, Hideaki, Oka, Hideaki, Nishida, Yusuke, Ishii, Koji, Ooki, Takao, Nidaira, Yuki, Asami, Takahiro, Jinta, Torahiko, Nakamura, Akira, Taniyama, Daisuke, Yamamoto, Kei, Tanaka, Katsushi, Ueshima, Kankuro, Fuwa, Tetsuji, Stucky, Ashley, Suzuki, Tadaki, Smith, Chris, Hibberd, Martin, Ariyoshi, Koya, and Suzuki, Motoi

Published
2023
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7. Age-Stratified Seroprevalence of SARS-CoV-2 Antibodies before and during the Vaccination Era, Japan, February 2020-March 2022

Author

Yamayoshi, Seiya, Iwatsuki-Horimoto, Kiyoko, Okuda, Moe, Ujie, Michiko, Yasuhara, Atsuhiro, Murakami, Jurika, Duong, Calvin, Hamabata, Taiki, Ito, Mutsumi, Chiba, Shiho, Kobayashi, Ryo, Takahashi, Satoshi, Mitamura, Keiko, Hagihara, Masao, Shibata, Akimichi, Uwamino, Yoshifumi, Hasegawa, Naoki, Ebina, Toshiaki, Izumi, Akihiko, Kato, Hideaki, Nakajima, Hideaki, Sugaya, Norio, Seki, Yuki, Iqbal, Asef, Kamimaki, Isamu, Yamazaki, Masahiko, Kawaoka, Yoshihiro, and Furuse, Yuki

Subjects
Age factors in disease -- Analysis, Prevalence studies (Epidemiology) -- Methods, Health
Abstract

SARS-CoV-2, the etiologic agent of COVID-19, emerged at the end of 2019 and caused a pandemic. As of April 2022, despite the development of effective vaccines and therapeutics, >500 million [...]

Published
2022
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8. Differences among epitopes recognized by neutralizing antibodies induced by SARS-CoV-2 infection or COVID-19 vaccination

Author

Yamamoto, Shinya, Yamayoshi, Seiya, Ito, Mutsumi, Sakai-Tagawa, Yuko, Nakachi, Ichiro, Baba, Rie, Kamimoto, Shigenobu, Ogura, Takayuki, Hagiwara, Shigehiro, Kato, Hideaki, Nakajima, Hideaki, Uwamino, Yoshifumi, Yagi, Kazuma, Sugaya, Norio, Nagai, Hiroyuki, Saito, Makoto, Adachi, Eisuke, Koga, Michiko, Tsutsumi, Takeya, Duong, Calvin, Okuda, Moe, Murakami, Jurika, Furusawa, Yuri, Ujie, Michiko, Iwatsuki-Horimoto, Kiyoko, Yotsuyanagi, Hiroshi, and Kawaoka, Yoshihiro

Published
2023
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9. SARS-CoV-2 spike protein antibody titers 6 months after SARS-CoV-2 mRNA vaccination among patients undergoing hemodialysis in Japan

Author

Kanai, Daisuke, Wakui, Hiromichi, Haze, Tatsuya, Azushima, Kengo, Kinguchi, Sho, Tsukamoto, Shunichiro, Kanaoka, Tomohiko, Urate, Shingo, Toya, Yoshiyuki, Hirawa, Nobuhito, Kato, Hideaki, Watanabe, Fumimasa, Hanaoka, Kanako, Hanaoka, Masaaki, Mitsuhashi, Hiroshi, Yamaguchi, Satoshi, Ohnishi, Toshimasa, and Tamura, Kouichi

Published
2022
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11. Compassionate Use of Remdesivir for Patients with Severe Covid-19

Author

Grein, Jonathan, Ohmagari, Norio, Shin, Daniel, Diaz, George, Asperges, Erika, Castagna, Antonella, Feldt, Torsten, Green, Gary, Green, Margaret L, Lescure, François-Xavier, Nicastri, Emanuele, Oda, Rentaro, Yo, Kikuo, Quiros-Roldan, Eugenia, Studemeister, Alex, Redinski, John, Ahmed, Seema, Bernett, Jorge, Chelliah, Daniel, Chen, Danny, Chihara, Shingo, Cohen, Stuart H, Cunningham, Jennifer, D'Arminio Monforte, Antonella, Ismail, Saad, Kato, Hideaki, Lapadula, Giuseppe, L'Her, Erwan, Maeno, Toshitaka, Majumder, Sumit, Massari, Marco, Mora-Rillo, Marta, Mutoh, Yoshikazu, Nguyen, Duc, Verweij, Ewa, Zoufaly, Alexander, Osinusi, Anu O, DeZure, Adam, Zhao, Yang, Zhong, Lijie, Chokkalingam, Anand, Elboudwarej, Emon, Telep, Laura, Timbs, Leighann, Henne, Ilana, Sellers, Scott, Cao, Huyen, Tan, Susanna K, Winterbourne, Lucinda, Desai, Polly, Mera, Robertino, Gaggar, Anuj, Myers, Robert P, Brainard, Diana M, Childs, Richard, and Flanigan, Timothy

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Emerging Infectious Diseases, Lung, Clinical Trials and Supportive Activities, Clinical Research, Prevention, Infectious Diseases, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Adenosine Monophosphate, Administration, Intravenous, Adult, Aged, Aged, 80 and over, Alanine, Antiviral Agents, Betacoronavirus, COVID-19, Canada, Compassionate Use Trials, Coronavirus Infections, Europe, Female, Humans, Japan, Male, Middle Aged, Pandemics, Pneumonia, Viral, Respiration, Artificial, SARS-CoV-2, United States, Young Adult, COVID-19 Drug Treatment, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundRemdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2.MethodsWe provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day.ResultsOf the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation.ConclusionsIn this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).

Published
2020

12. Multi-omics of NET formation and correlations with CNDP1, PSPB, and L-cystine levels in severe and mild COVID-19 infections

Author

Bramer, Lisa M., Hontz, Robert D., Eisfeld, Amie J., Sims, Amy C., Kim, Young-Mo, Stratton, Kelly G., Nicora, Carrie D., Gritsenko, Marina A., Schepmoes, Athena A., Akasaka, Osamu, Koga, Michiko, Tsutsumi, Takeya, Nakamura, Morio, Nakachi, Ichiro, Baba, Rie, Tateno, Hiroki, Suzuki, Shoji, Nakajima, Hideaki, Kato, Hideaki, Ishida, Kazunari, Ishii, Makoto, Uwamino, Yoshifumi, Mitamura, Keiko, Paurus, Vanessa L., Nakayasu, Ernesto S., Attah, Isaac K., Letizia, Andrew G., Waters, Katrina M., Metz, Thomas O., Corson, Karen, Kawaoka, Yoshihiro, Gerbasi, Vincent R., Yotsuyanagi, Hiroshi, and Iwatsuki-Horimoto, Kiyoko

Published
2023
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13. Structural basis for ion selectivity in potassium-selective channelrhodopsins

Author

Tajima, Seiya, Kim, Yoon Seok, Fukuda, Masahiro, Jo, YoungJu, Wang, Peter Y., Paggi, Joseph M., Inoue, Masatoshi, Byrne, Eamon F.X., Kishi, Koichiro E., Nakamura, Seiwa, Ramakrishnan, Charu, Takaramoto, Shunki, Nagata, Takashi, Konno, Masae, Sugiura, Masahiro, Katayama, Kota, Matsui, Toshiki E., Yamashita, Keitaro, Kim, Suhyang, Ikeda, Hisako, Kim, Jaeah, Kandori, Hideki, Dror, Ron O., Inoue, Keiichi, Deisseroth, Karl, and Kato, Hideaki E.

Published
2023
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14. Newly developed artificial intelligence algorithm for COVID-19 pneumonia: utility of quantitative CT texture analysis for prediction of favipiravir treatment effect

Author

Ohno, Yoshiharu, Aoyagi, Kota, Arakita, Kazumasa, Doi, Yohei, Kondo, Masashi, Banno, Sumi, Kasahara, Kei, Ogawa, Taku, Kato, Hideaki, Hase, Ryota, Kashizaki, Fumihiro, Nishi, Koichi, Kamio, Tadashi, Mitamura, Keiko, Ikeda, Nobuhiro, Nakagawa, Atsushi, Fujisawa, Yasuko, Taniguchi, Akira, Ikeda, Hirotaka, Hattori, Hidekazu, Murayama, Kazuhiro, and Toyama, Hiroshi

Published
2022
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15. Characterization of a new SARS-CoV-2 variant that emerged in Brazil

Author

Imai, Masaki, Halfmann, Peter J., Yamayoshi, Seiya, Iwatsuki-Horimoto, Kiyoko, Chiba, Shiho, Watanabe, Tokiko, Nakajima, Noriko, Ito, Mutsumi, Kuroda, Makoto, Kiso, Maki, Maemura, Tadashi, Takahashi, Kenta, Loeber, Samantha, Hatta, Masato, Koga, Michiko, Nagai, Hiroyuki, Yamamoto, Shinya, Saito, Makoto, Adachi, Eisuke, Akasaka, Osamu, Nakamura, Morio, Nakachi, Ichiro, Ogura, Takayuki, Baba, Rie, Fujita, Kensuke, Ochi, Junichi, Mitamura, Keiko, Kato, Hideaki, Nakajima, Hideaki, Yagi, Kazuma, Hattori, Shin-ichiro, Maeda, Kenji, Suzuki, Tetsuya, Miyazato, Yusuke, Valdez, Riccardo, Gherasim, Carmen, Furusawa, Yuri, Okuda, Moe, Ujie, Michiko, Lopes, Tiago J. S., Yasuhara, Atsuhiro, Ueki, Hiroshi, Sakai-Tagawa, Yuko, Eisfeld, Amie J., Baczenas, John J., Baker, David A., O’Connor, Shelby L., O’Connor, David H., Fukushi, Shuetsu, Fujimoto, Tsuguto, Kuroda, Yudai, Gordon, Aubree, Maeda, Ken, Ohmagari, Norio, Sugaya, Norio, Yotsuyanagi, Hiroshi, Mitsuya, Hiroaki, Suzuki, Tadaki, and Kawaoka, Yoshihiro

Published
2021

16. Clinical characteristics and genome epidemiology of Stenotrophomonas maltophilia in Japan

Author

Hase, Ryota, primary, Sakurai, Aki, additional, Suzuki, Masahiro, additional, Itoh, Naoya, additional, Hayakawa, Kayoko, additional, Uemura, Kohei, additional, Matsumura, Yasufumi, additional, Kato, Hideaki, additional, Ishihara, Takuma, additional, van Duin, David, additional, Ohmagari, Norio, additional, Doi, Yohei, additional, and Saito, Sho, additional

Published
2024
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17. Clinical characteristics and treatment outcomes of carbapenem-resistant Enterobacterales infections in Japan

Author

Oka, Keisuke, Matsumoto, Akane, Tetsuka, Nobuyuki, Morioka, Hiroshi, Iguchi, Mitsutaka, Ishiguro, Nobuhisa, Nagamori, Tsunehisa, Takahashi, Satoshi, Saito, Norihiro, Tokuda, Koichi, Igari, Hidetoshi, Fujikura, Yuji, Kato, Hideaki, Kanai, Shinichiro, Kusama, Fumiko, Iwasaki, Hiromichi, Furuhashi, Kazuki, Baba, Hisashi, Nagao, Miki, Nakanishi, Masaki, Kasahara, Kei, Kakeya, Hiroshi, Chikumi, Hiroki, Ohge, Hiroki, Azuma, Momoyo, Tauchi, Hisamichi, Shimono, Nobuyuki, Hamada, Yohei, Takajo, Ichiro, Nakata, Hirotomo, Kawamura, Hideki, Fujita, Jiro, and Yagi, Tetsuya

Published
2022
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19. Structure–Function Relationship of Channelrhodopsins

Author

Kato, Hideaki E., Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Yawo, Hiromu, editor, Kandori, Hideki, editor, Koizumi, Amane, editor, and Kageyama, Ryoichiro, editor

Published
2021
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25. HLA‐DQA1*01:03 and DQB1*06:01 are risk factors for severe COVID‐19 pneumonia.

Author

Tanaka, Katsushi, Meguro, Akira, Hara, Yu, Endo, Lisa, Izawa, Ami, Muraoka, Suguru, Kaneko, Ayami, Somekawa, Kohei, Hirata, Momo, Otsu, Yukiko, Matsumoto, Hiromi, Nagasawa, Ryo, Kubo, Sosuke, Murohashi, Kota, Aoki, Ayako, Fujii, Hiroaki, Watanabe, Keisuke, Horita, Nobuyuki, Kato, Hideaki, and Kobayashi, Nobuaki

Subjects
HAPLOTYPES, JAPANESE people, SARS-CoV-2 Omicron variant, LINKAGE disequilibrium, RESPIRATORY insufficiency
Abstract

The clinical spectrum of COVID‐19 includes a wide range of manifestations, from mild symptoms to severe pneumonia. HLA system plays a pivotal role in immune responses to infectious diseases. The purpose of our study was to investigate the association between HLA and COVID‐19 severity in a Japanese population. The study included 209 Japanese COVID‐19 patients aged ≥20 years. Saliva samples were collected and used to determine the HLA genotype by HLA imputation through genome‐wide association analyses. The association between HLA genotype and COVID‐19 severity was then evaluated. The allele frequency was compared between patients with respiratory failure (severe group: 91 cases) and those without respiratory failure (non‐severe group: 118 cases), categorising the data into three time periods: pre‐Omicron epidemic period, Omicron epidemic period, and total period of this study (from January 2021 to May 2023). In comparing the severe and non‐severe groups, the frequencies of the HLA‐DQA1*01:03 (35.1% vs. 10.5%, odds ratio [OR] = 4.57, corrected p [pc] = 0.041) and ‐DQB1*06:01 (32.4% vs. 7.9%, OR = 5.54, pc = 0.030) alleles were significantly higher in the severe group during the pre‐Omicron epidemic period. During the Omicron epidemic period, HLA‐DQB1*06 (32.4% vs. 7.9%, OR = 5.54, pc = 0.030) was significantly higher in the severe group. During total period of this study, HLA‐DQA1*01:03 (30.2% vs. 14.4%, OR = 2.57, corrected pc = 0.0013) and ‐DQB1*06:01 (44.5% vs. 26.7%, OR = 2.20, pc = 0.013) alleles were significantly higher in the severe group. HLA‐DQB1*06:01 and ‐DQA1*01:03 were in strong linkage disequilibrium with each other (r2 = 0.91) during total period of this study, indicating that these two alleles form a haplotype. The frequency of the HLA‐DQA1*01:03–DQB1*06:01 in the severe group was significantly higher than in the non‐severe group during pre‐Omicron epidemic period (32.4% vs. 7.9%, OR = 5.59, pc = 0.00072), and total period of this study (28.6% vs. 13.1%, OR = 2.63, pc = 0.0013). During Omicron epidemic period, the haplotype did not demonstrate statistical significance, although the odds ratio indicated a value greater 1. Frequencies of the HLA‐DQA1*01:03 and ‐DQB1*06:01 alleles were significantly higher in severe COVID‐19 patients, suggesting that these alleles are risk factors for severe COVID‐19 pneumonia in the Japanese population. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Antibody titers against SARS-CoV-2 decline, but do not disappear for several months

Author

Yamayoshi, Seiya, Yasuhara, Atsuhiro, Ito, Mutsumi, Akasaka, Osamu, Nakamura, Morio, Nakachi, Ichiro, Koga, Michiko, Mitamura, Keiko, Yagi, Kazuma, Maeda, Kenji, Kato, Hideaki, Nojima, Masanori, Pattinson, David, Ogura, Takayuki, Baba, Rie, Fujita, Kensuke, Nagai, Hiroyuki, Yamamoto, Shinya, Saito, Makoto, Adachi, Eisuke, Ochi, Junichi, Hattori, Shin-ichiro, Suzuki, Tetsuya, Miyazato, Yusuke, Chiba, Shiho, Okuda, Moe, Murakami, Jurika, Hamabata, Taiki, Iwatsuki-Horimoto, Kiyoko, Nakajima, Hideaki, Mitsuya, Hiroaki, Omagari, Norio, Sugaya, Norio, Yotsuyanagi, Hiroshi, and Kawaoka, Yoshihiro

Published
2021
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30. Response to RMED-D-22–00,258.R1

Author

Ohno, Yoshiharu, Aoyagi, Kota, Arakita, Kazumasa, Doi, Yohei, Kondo, Masashi, Banno, Sumi, Kasahara, Kei, Ogawa, Taku, Kato, Hideaki, Hase, Ryota, Kashizaki, Fumihiro, Nishi, Koichi, Kamio, Tadashi, Mitamura, Keiko, Ikeda, Nobuhiro, Nakagawa, Atsushi, Fujisawa, Yasuko, Taniguchi, Akira, Ikeda, Hidetake, Hattori, Hidekazu, Murayama, Kazuhiro, and Toyama, Hiroshi

Published
2022
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35. 719. Stenotrophomonas maltophilia in Japanese hospitals: Clinical characteristics and molecular epidemiology of infection and colonization cases registered in multicenter surveillance network

Author

Hase, Ryota, primary, Sakurai, Aki, additional, Suzuki, Masahiro, additional, Itoh, Naoya, additional, Saito, Sho, additional, Hayakawa, Kayoko, additional, Uemura, Kohei, additional, Matsumara, Yasufumi, additional, Kato, Hideaki, additional, van Duin, David, additional, Ohmagari, Norio, additional, and Doi, Yohei, additional

Published
2023
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36. 371. Clinical Characteristics and Prognoses for Carbapenem-Resistant Bacterial Infections in Patients with Cancer in Japan: A Multicenter Study from the Multi-Drug Resistant Organisms Clinical Research Network (MDRnet)

Author

Itoh, Naoya, primary, Kawabata, Takanori, additional, Akazawa, Nana, additional, Hayakawa, Kayoko, additional, Suzuki, Masahiro, additional, Sakurai, Aki, additional, Uemura, Kohei, additional, Matsumara, Yasufumi, additional, Hase, Ryota, additional, Kato, Hideaki, additional, Hashimoto, Takehiro, additional, Matono, Takashi, additional, van Duin, David, additional, Ohmagari, Norio, additional, Doi, Yohei, additional, and Saito, Sho, additional

Published
2023
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43. Performance of laboratory tests for detection for Clostridioides difficile: A multicenter prospective study in Japan

Author

Senoh, Mitsutoshi, Kato, Haru, Honda, Hitoshi, Fukuda, Tadashi, Tagashira, Yasuaki, Horiuchi, Hiroko, Chiba, Hiroshi, Suzuki, Daisuke, Hosokawa, Naoto, Kitazono, Hidetaka, Norisue, Yasuhiro, Kume, Hisashi, Mori, Nobuaki, Morikawa, Hideo, Kashiwagura, Saeko, Higuchi, Akiko, Kato, Hideaki, Nakamura, Makoto, Ishiguro, Saori, Morita, Sayuri, Ishikawa, Hideaki, Watanabe, Takuya, Kojima, Katsuyuki, Yokomaku, Izumi, Bando, Tatsuya, Toimoto, Kayoko, Moriya, Kei, Kasahara, Kei, Kitada, Seigo, Ogawa, Junko, Saito, Haruko, Tominaga, Harumi, Shimizu, Yousuke, Masumoto, Fumi, Tadera, Kayoko, Yoshida, Junichi, Kikuchi, Tetsuya, Yoshikawa, Ichiro, Watanabe, Tatsuyuki, Honda, Masahisa, Yokote, Kuniko, Toyokawa, Takao, Miyazato, Hiroko, Nakama, Mika, Mahe, Cedric, Reske, Kimberly, Olsen, Margaret A., and Dubberke, Erik R.

Published
2019
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44. Clostridioides (Clostridium) difficile infection burden in Japan: A multicenter prospective study

Author

Kato, Haru, Senoh, Mitsutoshi, Honda, Hitoshi, Fukuda, Tadashi, Tagashira, Yasuaki, Horiuchi, Hiroko, Chiba, Hiroshi, Suzuki, Daisuke, Hosokawa, Naoto, Kitazono, Hidetaka, Norisue, Yasuhiro, Kume, Hisashi, Mori, Nobuaki, Morikawa, Hideo, Kashiwagura, Saeko, Higuchi, Akiko, Kato, Hideaki, Nakamura, Makoto, Ishiguro, Saori, Morita, Sayuri, Ishikawa, Hideaki, Watanabe, Takuya, Kojima, Katsuyuki, Yokomaku, Izumi, Bando, Tatsuya, Toimoto, Kayoko, Moriya, Kei, Kasahara, Kei, Kitada, Seigo, Ogawa, Junko, Saito, Haruko, Tominaga, Harumi, Shimizu, Yousuke, Masumoto, Fumi, Tadera, Kayoko, Yoshida, Junichi, Kikuchi, Tetsuya, Yoshikawa, Ichiro, Watanabe, Tatsuyuki, Honda, Masahisa, Yokote, Kuniko, Toyokawa, Takao, Miyazato, Hiroko, Nakama, Mika, Mahe, Cedric, Reske, Kimberly, Olsen, Margaret A., and Dubberke, Erik R.

Published
2019
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45. Structure of the neurotensin receptor 1 in complex with [beta]-arrestin 1

Author

Huang, Weijiao, Masureel, Matthieu, Qu, Qianhui, Janetzko, John, Inoue, Asuka, Kato, Hideaki E., and Robertson, Michael J.

Subjects
Arrestins -- Observations -- Analysis, Neurotensin -- Structure, G proteins -- Analysis, Phosphorylation -- Influence -- Analysis, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Arrestin proteins bind to active, phosphorylated G-protein-coupled receptors (GPCRs), thereby preventing G-protein coupling, triggering receptor internalization and affecting various downstream signalling pathways.sup.1,2. Although there is a wealth of structural information detailing the interactions between GPCRs and G proteins, less is known about how arrestins engage GPCRs. Here we report a cryo-electron microscopy structure of full-length human neurotensin receptor 1 (NTSR1) in complex with truncated human [beta]-arrestin 1 ([beta]arr1([DELTA]CT)). We find that phosphorylation of NTSR1 is critical for the formation of a stable complex with [beta]arr1([DELTA]CT), and identify phosphorylated sites in both the third intracellular loop and the C terminus that may promote this interaction. In addition, we observe a phosphatidylinositol-4,5-bisphosphate molecule forming a bridge between the membrane side of NTSR1 transmembrane segments 1 and 4 and the C-lobe of arrestin. Compared with a structure of a rhodopsin-arrestin-1 complex, in our structure arrestin is rotated by approximately 85° relative to the receptor. These findings highlight both conserved aspects and plasticity among arrestin-receptor interactions. A cryo-electron microscopy structure of the neurotensin receptor 1 in complex with [beta]-arrestin 1 is reported., Author(s): Weijiao Huang [sup.1] , Matthieu Masureel [sup.1] , Qianhui Qu [sup.1] [sup.2] , John Janetzko [sup.1] , Asuka Inoue [sup.3] , Hideaki E. Kato [sup.1] [sup.6] , Michael J. [...]

Published
2020
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46. Structural insights into µ-opioid receptor activation

Author

Huang, Weijiao, Manglik, Aashish, Venkatakrishnan, AJ, Laeremans, Toon, Feinberg, Evan N, Sanborn, Adrian L, Kato, Hideaki E, Livingston, Kathryn E, Thorsen, Thor S, Kling, Ralf C, Granier, Sébastien, Gmeiner, Peter, Husbands, Stephen M, Traynor, John R, Weis, William I, Steyaert, Jan, Dror, Ron O, and Kobilka, Brian K

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Chemical Sciences, Pharmacology and Pharmaceutical Sciences, Biotechnology, Neurosciences, Generic health relevance, Allosteric Regulation, Animals, Binding Sites, Crystallography, X-Ray, Heterotrimeric GTP-Binding Proteins, Mice, Models, Molecular, Molecular Dynamics Simulation, Morphinans, Protein Stability, Protein Structure, Tertiary, Pyrroles, Receptor, Muscarinic M2, Receptors, Adrenergic, beta-2, Receptors, Opioid, mu, Single-Chain Antibodies, Structure-Activity Relationship, General Science & Technology
Abstract

Activation of the μ-opioid receptor (μOR) is responsible for the efficacy of the most effective analgesics. To shed light on the structural basis for μOR activation, here we report a 2.1 Å X-ray crystal structure of the murine μOR bound to the morphinan agonist BU72 and a G protein mimetic camelid antibody fragment. The BU72-stabilized changes in the μOR binding pocket are subtle and differ from those observed for agonist-bound structures of the β2-adrenergic receptor (β2AR) and the M2 muscarinic receptor. Comparison with active β2AR reveals a common rearrangement in the packing of three conserved amino acids in the core of the μOR, and molecular dynamics simulations illustrate how the ligand-binding pocket is conformationally linked to this conserved triad. Additionally, an extensive polar network between the ligand-binding pocket and the cytoplasmic domains appears to play a similar role in signal propagation for all three G-protein-coupled receptors.

Published
2015

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