Cryptides : elucidation of regulatory mechanisms by functional peptides hidden in protein structures

2011 Fiscal Year Final Research Report

• Project/Area Number: 21603014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Nagahama Institute of Bio-Science and Technology (2011); Kyoto Pharmaceutical University (2009-2010)
• Principal Investigator: MUKAI Hidehito 長浜バイオ大学, バイオサイエンス学部, 准教授 (20251027)
• Co-Investigator(Kenkyū-buntansha): KISO Yoshiaki 長浜バイオ大学, バイオサイエンス学部, 客員教授 (40089107)
• Project Period (FY): 2009 – 2011
• Keywords: クリプタイド / マイトクリプタイド / 生理活性ペプチド / Gタンパク質 / Gタンパク質共役受容体 / 好中球 / バイオインフォマティクス / 自然免疫

Research Abstract

Here, we discovered that many fragmented peptides simultaneously produced during maturation and degradation processes of functional proteins and bioactive peptides have efficient physiological activities although these fragmented peptides have long been thought that they had no biological significance. We purified and identified novel functional peptides hidden in mitochondrial proteins mitocryptide-2 and-3 that activated neutrophils at nanomolar concentrations from porcine hearts. The receptor molecules and the intracellular signal mechanisms for these mitocryptides were also elucidated.

Research Products

• [Journal Article] クリプタイド:タンパク質に隠された新しい生理活性ペプチド.その発見と存在意義および効率的スクリーニング (2012)
  • Author(s): 向井秀仁、木曽良明
  • Journal Title: 遺伝子医学MOOK Volume: Vol.21 Pages: 298-304
  • Peer Reviewed
• [Journal Article] Isolation and identification of novel neutrophil-activating cryptides hidden in mitochondrial cytochrome c (2012)
  • Author(s): Hokari, Y., Seki, T., Nakano, H., Matsuo, Y., Fukamizu, A., Munekata, E., Kiso, Y., and Mukai, H
  • Journal Title: Protein and Peptide Letters Volume: Vol.19 Pages: 680-687
  • URL: http://www.benthamdirect.org/pages/content.php?PPL/2012/00000019/00000006/0015E.SGM
  • Peer Reviewed
• [Journal Article] Novel neutrophil-activating cryptides hidden in mitochondrial cytochrome c : identification and structure-activity studies (2012)
  • Author(s): Hokari, Y., Seki, T., Nakano, H., Fukamizu, A., Munekata, E., Kiso, Y., and Mukai, H.
  • Journal Title: Peptide Science Volume: Vol.2011 Pages: 61-62
  • Peer Reviewed
• [Journal Article] Cryptides and their accumulative signaling : a novel regulatory mechanism by functional peptides hidden in protein structures (2011)
  • Author(s): Mukai, H. and Kiso, Y.
  • Journal Title: Peptides Volume: Vol.2011 Pages: 314-315
  • Peer Reviewed
• [Journal Article] Click peptide : application to E22-type mutant of amyloid (2011)
  • Author(s): Wang, H., Sohma, Y., Taniguchi, A., Hirayama, Y., Kakizawa, T., Mukai, H., and Kiso, Y.
  • Journal Title: peptide, Peptide Science Volume: Vol.2010 Pages: 221
  • Peer Reviewed
• [Journal Article] Click peptide : In situ production of pyroGlu-Abeta from the O-acyl isopeptide (2011)
  • Author(s): Yamazaki, M., Sohma, Y., Taniguchi, A., Hirayama, Y., Furuya, M., Mukai, H., and Kiso, Y.
  • Journal Title: Peptide Science Volume: Vol.2010 Pages: 210
  • Peer Reviewed
• [Journal Article] Use of O-acyl isopeptides to identify new functions of amyloid. peptides (2011)
  • Author(s): Sohma, Y., Taniguchi, A., Hirayama, Y., Wang, H., Yamazaki, M., Mukai, H., and Kiso, Y.
  • Journal Title: Peptide Science Volume: Vol.2010 Pages: 54
  • Peer Reviewed
• [Journal Article] Cryptides : non-classical bioactive peptides hidden in protein structures (2011)
  • Author(s): Mukai, H., Seki, T., Hokari, Y., Fukamizu, A., and Kiso, Y.
  • Journal Title: Peptide Science Volume: Vol.2010 Pages: 29
  • Peer Reviewed
• [Journal Article] Self-assembly pathways of E22Δ-type amyloid. peptide mutants generated from non-aggregative O-acyl isopeptide precursors (2011)
  • Author(s): Sohma, Y., Wang, H., Taniguchi, A., Hirayama, Y., Kakizawa, T., Yamazaki, M., Mukai, H., and Kiso, Y.
  • Journal Title: Bioorganic and Medicinal Chemistry Volume: Vol.19 Pages: 3787-3792
  • DOI: DOI:10.1016/j.bmc.2011.04.056
  • Peer Reviewed
• [Journal Article] Click peptide' using production of monomer A. from the O-acyl isopeptide : Application to assay system of aggregation inhibitors and cellular cytotoxicity (2011)
  • Author(s): Sohma, Y., Hirayama, Y., Taniguchi, A., Mukai, H., and Kiso, Y.
  • Journal Title: Bioorganic and Medicinal Chemistry Volume: Vol.19 Pages: 1729-1733
  • DOI: DOI:10.1016/j.bmc.2011.01.021
  • Peer Reviewed
• [Journal Article] Mitocryptide-2, a neutrophil-activating cryptide, is a specific endogenous agonist for fromyl-peptide receptor-like 1 (2011)
  • Author(s): Seki, T., Fukamizu, A., Kiso, Y., and Mukai, H.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: Vol.404 Pages: 482-487
  • DOI: DOI:10.1016/j.bbrc.2010.12.007
  • Peer Reviewed
• [Journal Article] クリプタイドの発見と新しい生体情報伝達機構 (2010)
  • Author(s): 向井秀仁、木曽良明、若松馨
  • Journal Title: 生化学 Volume: Vol.82 Pages: 524-532
  • URL: http://wwwsoc.nii.ac.jp/jbiochem/magazine/82-06-09.pdf
  • Peer Reviewed
• [Journal Article] Cryptides : receptors and signaling mechanisms for novel neutrophil-activating peptides hidden in mitochondrial proteins (2010)
  • Author(s): Mukai, H., Seki, T., Hokari, Y., Fukamizu, A., and Kiso, Y.
  • Journal Title: Peptides Volume: Vol.2010 Pages: 36-37
  • Peer Reviewed
• [Journal Article] Click peptide : Water-soluble precursor producing monomer amyloid. peptide in situ (2010)
  • Author(s): Hirayama, Y., Taniguchi, A., Sohma, Y., Mukai, H., Kimura, T., Hayashi, Y., Matsuzaki, K., and Kiso, Y.
  • Journal Title: Peptide Science Volume: Vol.2009 Pages: 371-372
  • Peer Reviewed
• [Journal Article] Investigation of A. 1. 42 mutants based on O-acyl isopeptide method ; Synthesis of O-acyl isopeptides and in situ production of their native forms (2010)
  • Author(s): Wang, H., Kakizawa, T., Taniguchi, A., Mizuguchi, T., Sohma, Y., Mukai, H., Kimura, T., and Kiso, Y.
  • Journal Title: Peptide Science Volume: Vol.2009 Pages: 367-368
  • Peer Reviewed
• [Journal Article] Characterization of receptors and signaling mechanisms for mitocryptide-2, a novel cryptide that activates neutrophils (2010)
  • Author(s): Mukai, H., Seki, T., Hokari, Y., Fukamizu, A., and Kiso, Y.
  • Journal Title: Peptide Science Volume: Vol.2009 Pages: 97-98
  • Peer Reviewed
• [Journal Article] Cryptides : Discovery of functional cryptic peptides hidden in protein structures and identification of their signaling mechanisms (2010)
  • Author(s): Mukai, H., Seki, T., Munekata, E., and Kiso, Y.
  • Journal Title: Peptides Volume: Vol.2009 Pages: 203-204
  • Peer Reviewed
• [Journal Article] Click peptide "based on" O-acyl isopeptide method": In situ production of monomer amyloid. Peptide from water-soluble precursor analogue (2010)
  • Author(s): Taniguchi, A., Sohma, Y., Skwarczynski, M., Hirayama, Y., Okada, T., Ikeda, K., Prakash, H., Mukai, H., Kimura, T., Hayashi, Y., Hirota, S., Matsuzaki, K., and Kiso, Y.
  • Journal Title: Peptides Volume: Vol.2009 Pages: 195-196
  • Peer Reviewed
• [Journal Article] Prevention of peptide aggregation by non-detergent sulfobetaines(NDSBs) (2009)
  • Author(s): Wakamatsu, K., Takei, A., Inaoka, Y., Xian, L., Kobori, K., Kato, S., Mukai, H., Kohno, T., and Nameki, N.
  • Journal Title: Peptide Science Volume: Vol.2008 Pages: 397-400
  • Peer Reviewed
• [Journal Article] Cryptide signaling and exocytotic mechanisms induced by amphiphilic peptides (2009)
  • Author(s): Mukai, H., Ueki, N., Someya, K., Kawanami, M., Matsuo, Y., Kiyama, M., Kamijo, R., Kikichi, M., Fukuhara, S., Munekata, E., and Kiso, Y.
  • Journal Title: Peptide Science Volume: Vol.2008 Pages: 307-310
  • Peer Reviewed
• [Journal Article] Click peptide by use of the O-acyl isopeptide method : production of amyloid. peptide from water-soluble analogue (2009)
  • Author(s): Taniguchi, A., Sohma, Y., Skwarczynski, M., Okada, T., Ikeda, K., Prakash, H., Mukai, H., Kimura, T., Hayashi, Y., Hirota, S., Matsuzaki, K., and Kiso, Y.
  • Journal Title: Peptide Science Volume: Vol.2008 Pages: 121-122
  • Peer Reviewed
• [Journal Article] Cryptide signal : a novel signaling mechanisms involving cryptides (2009)
  • Author(s): Mukai, H., Ueki, N., Wakamatsu, K., and Kiso, Y.
  • Journal Title: Peptides Volume: Vol.2008 Pages: 570-571
  • Peer Reviewed
• [Journal Article] Development of water-soluble click peptides by use of the O-acyl isopeptide method : In situ production of Alzheimer's amyloid (2009)
  • Author(s): Taniguchi, A., Sohma, Y., Skwarczynski, M., Nagano, T., Okada, T., Ikeda, K., Prakash, H., Mukai, H., Hayashi, Y., Kimura, T., Hirota, S., Matsuzaki, K., and Kiso, Y.
  • Journal Title: peptide, Peptides Volume: Vol.2008 Pages: 32-33
  • Peer Reviewed
• [Journal Article] Mitocryptide-2 : purification, identification and characterization of a novel cryptide that activates neutrophils (2009)
  • Author(s): Mukai, H., Seki, T., Nakano, H., Hokari, Y., Takao, T., Kawanami, M., Tsukagoshi, H., Kimura, H., Kiso, Y., Shimonishi, Y., Nishi, Y., and Munekata, E
  • Journal Title: Journal of Immunology Volume: Vol.182 Pages: 5072-5080
  • DOI: DOI:10.4049/jimmunol.0802965
  • Peer Reviewed
• [Journal Article] Click peptide : pH-triggered in situ production and aggregation of monomer A. 1-42 (2009)
  • Author(s): Taniguchi, A., Sohma, Y., Hirayama, Y., Mukai, H., Kimura, T., Hayashi, Y., Matsuzaki, K., and Kiso, Y.
  • Journal Title: Chem Bio Chem Volume: Vol.10 Pages: 710-715
  • DOI: DOI:10.1002/cbic.200800765)
  • Peer Reviewed
• [Presentation] クリプタイド(Cryptides):その存在意義と産業的応用 (2012)
  • Author(s): 向井秀仁
  • Organizer: 第15回ペプチドフォーラム
  • Place of Presentation: 長浜
  • Year and Date: 2012-03-16
• [Presentation] クリプタイド(Cryptides):タンパク質に隠された新しいタイプの生理活性ペプチド (2012)
  • Author(s): 向井秀仁
  • Organizer: 第2回滋賀県ライフサイエンスセミナー
  • Place of Presentation: 大津
  • Year and Date: 2012-01-30
• [Presentation] Mitocryptides : functional cryptic peptides hidden in mitochondrial protein structures and their possible applications (2011)
  • Author(s): Hidehito Mukai
  • Organizer: 14th Peptide Forum
  • Place of Presentation: 鹿児島
  • Year and Date: 2011-12-16
• [Presentation] Cryptides : Functional peptides hidden in protein structures and their possible applications (2011)
  • Author(s): Hidehito Mukai
  • Organizer: 9th Australian Peptide Conference
  • Place of Presentation: Hamilton Island, Australia
  • Year and Date: 2011-10-18
• [Presentation] Novel neutrophil-activating cryptides hidden in mitochondrial cytochrome c : identification and structure-activity studies (2011)
  • Author(s): Hidehito Mukai
  • Organizer: 第48回ペプチド討論会
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-27
• [Presentation] ミトコンドリアチトクロームcに隠された新規好中球活性化クリプタイドの単離・同定 (2011)
  • Author(s): 向井秀仁
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] Cryptides and their accumulative signaling : a novel regulatory mechanism by functional peptides hidden in protein structures (2011)
  • Author(s): Hidehito Mukai
  • Organizer: 22nd American Peptide Symposium
  • Place of Presentation: San Diego, USA
  • Year and Date: 2011-06-26
• [Presentation] タンパク質に隠された生理活性ペプチド「クリプタイド」が関わる新しい生体調節機構 (2011)
  • Author(s): 向井秀仁
  • Organizer: 日本ケミカルバイオロジー学会第6回年会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-24
• [Presentation] タンパク質に隠された新しい生理活性ペプチド、「クリプタイド(Cryptide)」 (2011)
  • Author(s): 向井秀仁
  • Organizer: 同定と生理機能.,大阪大学蛋白質研究所セミナー「ペプチド研究の新潮流:発見から応用へ」
  • Place of Presentation: 大阪
  • Year and Date: 2011-03-14
• [Presentation] Cryptides : Non-classical bioactive peptides hidden in protein structures (2010)
  • Author(s): Hidehito Mukai
  • Organizer: 5th International Peptide Symposium
  • Place of Presentation: 京都
  • Year and Date: 2010-12-07
• [Presentation] Mitocryptides : novel neutrophil-activating cryptides hidden in mitochondrial proteins (2010)
  • Author(s): Hidehito Mukai
  • Organizer: The 13th Akabori Conference(German-Japanese Symposium on Peptide Science)
  • Place of Presentation: Leipzig, Germany
  • Year and Date: 2010-09-13
• [Presentation] Cryptides : receptors and signaling mechanisms for novel neutrophil-activating peptides hidden in mitochondrial proteins (2010)
  • Author(s): Hidehito Mukai
  • Organizer: 31st European Peptide Symposium
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2010-09-09
• [Presentation] Mitocryptides : a novel family of neutrophil-activating peptides derived from mitochondrial proteins and their regulatory mechanisms (2010)
  • Author(s): Hidehito Mukai
  • Organizer: The 11th Chinese International Peptide Symposium
  • Place of Presentation: Lanzhou, China
  • Year and Date: 2010-07-07
• [Presentation] Clarification of signaling mechanisms for mitocryptides, novel neutrophil-activating peptides hidden in mitochondrial proteins (2010)
  • Author(s): Hidehito Mukai
  • Organizer: 12th Naples Workshop on Bioactive Peptides
  • Place of Presentation: Naples, Italy
  • Year and Date: 2010-06-06
• [Presentation] タンパク質に隠された生理活性ペプチド、「クリプタイド」を認識する受容体の同定および情報伝達機構の解析 (2010)
  • Author(s): 向井秀仁
  • Organizer: 日本ケミカルバイオロジー学会第5回年会
  • Place of Presentation: 横浜
  • Year and Date: 2010-05-19
• [Presentation] Characterization of signaling mechanisms for mitocryptides, novel neutrophil-activating cryptides isolated from porcine heart (2009)
  • Author(s): Hidehito Mukai
  • Organizer: 第32回日本分子生物学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] Cryptides : functional peptides hidden in protein structures-Discovery and physiological significance (2009)
  • Author(s): Hidehito Mukai
  • Organizer: 3rd Asia-Pacific International Peptide Symposium
  • Place of Presentation: Jeju, Korea
  • Year and Date: 2009-11-11
• [Presentation] 新規好中球活性化ペプチドmitocryptide-2の受容体と細胞内情報伝達機構の解析 (2009)
  • Author(s): 向井秀仁
  • Organizer: 第46回ペプチド討論会
  • Place of Presentation: 北九州
  • Year and Date: 2009-11-05
• [Presentation] タンパク質構造に隠された生理活性ペプチド、「クリプタイド」とその情報伝達機構「accumulative signaling」 (2009)
  • Author(s): 向井秀仁
  • Organizer: 第82回日本生化学会大会シンポジウム「ペプチドの多様性と機能」
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Presentation] タンパク質に隠された生理活性ペプチド「クリプタイド」の発見とその情報伝達機構 (2009)
  • Author(s): 向井秀仁
  • Organizer: 日本ケミカルバイオロジー学会第4回年会
  • Place of Presentation: 神戸
  • Year and Date: 2009-05-18
• [Remarks] 本研究に関する内容が日経バイオテクの上記ホームページおよび日経バイオテク誌(4-9, 2012)で紹介された。
  • URL: https://bio.nikkeibp.co.jp/article/news/20120321/160158/