MET-Activating Ubiquitin Multimers.
Growth Factors
Peptides
Protein Engineering
Receptors
Signal Transduction
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
04 09 2023
04 09 2023
Historique:
received:
22
05
2023
medline:
31
8
2023
pubmed:
14
7
2023
entrez:
14
7
2023
Statut:
ppublish
Résumé
Receptor tyrosine kinases (RTKs) are generally activated through their dimerization and/or oligomerization induced by their cognate ligands, and one such RTK hepatocyte growth factor (HGF) receptor, known as MET, plays an important role in tissue regeneration. Here we show the development of ubiquitin (Ub)-based protein ligand multimers, referred to as U-bodies, which act as surrogate agonists for MET and are derived from MET-binding macrocyclic peptides. Monomeric Ub constructs (U-body) were first generated by genetic implantation of a macrocyclic peptide pharmacophore into a structural loop of Ub (lasso-grafting) and subsequent optimization of its flanking spacer sequences via mRNA display. Such U-body constructs exhibit potent binding affinity to MET, thermal stability, and proteolytic stability. The U-body constructs also partially/fully inhibited or enhanced HGF-induced MET-phosphorylation. Their multimerization to dimeric, tetrameric, and octameric U-bodies linked by an appropriate peptide linker yielded potent MET activation activity and downstream cell proliferation-promoting activity. This work suggests that lasso-grafting of macrocycles to Ub is an effective approach to devising protein-based artificial RTK agonists and it can be useful in the development of a new class of biologics for various therapeutic applications.
Identifiants
pubmed: 37450419
doi: 10.1002/anie.202307157
doi:
Substances chimiques
Hepatocyte Growth Factor
67256-21-7
Ubiquitin
0
Proto-Oncogene Proteins c-met
EC 2.7.10.1
Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202307157Informations de copyright
© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
Références
M. A. Lemmon, J. Schlessinger, Cell 2010, 141, 1117-1134.
D. P. Bottaro, J. S. Rubin, D. L. Faletto, A. M.-L. Chan, T. E. Kmiecik, G. F. Vande Woude, S. A. Aaronson, Science 1991, 251, 802-804.
E. Uchikawa, Z. Chen, G.-Y. Xiao, X. Zhang, X. Bai, Nat. Commun. 2021, 12, 4074.
H. H. Niemann, Eur. J. Cell Biol. 2011, 90, 972-981.
L. Trusolino, A. Bertotti, P. M. Comoglio, Nat. Rev. Mol. Cell Biol. 2010, 11, 834-848.
K. Sakai, S. Aoki, K. Matsumoto, J. Biochem. 2015, 157, 271-284.
K. Matsumoto, H. Funakoshi, H. Takahashi, K. Sakai, Biomedicine 2014, 2, 275-300.
S. Hirano, A. Kawamoto, I. Tateya, M. Mizuta, Y. Kishimoto, N. Hiwatashi, Y. Kawai, T. Tsuji, R. Suzuki, M. Kaneko, Y. Naito, T. Kagimura, T. Nakamura, S. Kanemaru, J. Tissue Eng. Regener. Med. 2018, 12, 1031-1038.
N. Nagoshi, O. Tsuji, K. Kitamura, K. Suda, T. Maeda, Y. Yato, T. Abe, D. Hayata, M. Matsumoto, H. Okano, M. Nakamura, J. Neurotrauma 2020, 37, 1752-1758.
T. Nakamura, T. Nishizawa, M. Hagiya, T. Seki, M. Shimonishi, A. Sugimura, K. Tashiro, S. Shimizu, Nature 1989, 342, 440-443.
L. E. Donate, N. Srinivasan, R. Sowdhamini, E. Gherardi, T. L. Blundell, S. Aparicio, Protein Sci. 1994, 3, 2378-2394.
H. Wang, J. A. Keiser, Biochem. Biophys. Res. Commun. 2000, 272, 900-905.
D. Lietha, D. Y. Chirgadze, B. Mulloy, T. L. Blundell, E. Gherardi, EMBO J. 2001, 20, 5543-5555.
D. S. Jones, P.-C. Tsai, J. R. Cochran, Proc. Natl. Acad. Sci. USA 2011, 108, 13035-13040.
G. de Nola, B. Leclercq, A. Mougel, S. Taront, C. Simonneau, F. Forneris, E. Adriaenssens, H. Drobecq, L. Iamele, L. Dubuquoy, O. Melnyk, E. Gherardi, H. de Jonge, J. Vicogne, Life Sci. Alliance 2022, 5, e202201424.
R. Ueki, A. Ueki, N. Kanda, S. Sando, Angew. Chem. Int. Ed. 2016, 55, 579-582.
R. Ueki, S. Uchida, N. Kanda, N. Yamada, A. Ueki, M. Akiyama, K. Toh, H. Cabral, S. Sando, Sci. Adv. 2020, 6, eaay2801.
K. Ito, K. Sakai, Y. Suzuki, N. Ozawa, T. Hatta, T. Natsume, K. Matsumoto, H. Suga, Nat. Commun. 2015, 6, 6373.
E. Mihara, S. Watanabe, N. K. Bashiruddin, N. Nakamura, K. Matoba, Y. Sano, R. Maini, Y. Yin, K. Sakai, T. Arimori, K. Matsumoto, H. Suga, J. Takagi, Nat. Commun. 2021, 12, 1543.
Y. Komatsu, N. Terasaka, K. Sakai, E. Mihara, R. Wakabayashi, K. Matsumoto, D. Hilvert, J. Takagi, H. Suga, iScience 2021, 24, 103302.
K. Sakai, N. Sugano-Nakamura, E. Mihara, N. M. Rojas-Chaverra, S. Watanabe, H. Sato, R. Imamura, D. C.-C. Voon, I. Sakai, C. Yamasaki, C. Tateno, M. Shibata, H. Suga, J. Takagi, K. Matsumoto, Nat. Biomed. Eng. 2022, 7, 164-176.
Y. Yamagishi, I. Shoji, S. Miyagawa, T. Kawakami, T. Katoh, Y. Goto, H. Suga, Chem. Biol. 2011, 18, 1562-1570.
N. Sugano-Nakamura, K. Matoba, M. Hirose, N. K. Bashiruddin, Y. Matsunaga, K. Yamashita, K. Hirata, M. Yamamoto, T. Arimori, H. Suga, J. Takagi, Structure 2022, 30, 1411-1423.e4.
L. Radici, M. Bianchi, R. Crinelli, M. Magnani, Adv. Biosci. Biotechnol. 2013, 04, 1057-1062.
F. Job, F. Settele, S. Lorey, C. Rundfeldt, L. Baumann, A. G. Beck-Sickinger, U. Haupts, H. Lilie, E. Bosse-Doenecke, FEBS Open Bio 2015, 5, 579-593.
H. Yin, D. J. Craik, C. K. Wang, Angew. Chem. Int. Ed. 2019, 58, 7652-7656.
J. R. Kintzing, M. V. Filsinger Interrante, J. R. Cochran, Trends Pharmacol. Sci. 2016, 37, 993-1008.
T. Hey, E. Fiedler, R. Rudolph, M. Fiedler, Trends Biotechnol. 2005, 23, 514-522.
Y. Zhang, L. Zhou, L. Rouge, A. H. Phillips, C. Lam, P. Liu, W. Sandoval, E. Helgason, J. M. Murray, I. E. Wertz, J. E. Corn, Nat. Chem. Biol. 2013, 9, 51-58.
A. Ernst, G. Avvakumov, J. Tong, Y. Fan, Y. Zhao, P. Alberts, A. Persaud, J. R. Walker, A.-M. Neculai, D. Neculai, A. Vorobyov, P. Garg, L. Beatty, P.-K. Chan, Y.-C. Juang, M.-C. Landry, C. Yeh, E. Zeqiraj, K. Karamboulas, A. Allali-Hassani, M. Vedadi, M. Tyers, J. Moffat, F. Sicheri, L. Pelletier, D. Durocher, B. Raught, D. Rotin, J. Yang, M. F. Moran, S. Dhe-Paganon, S. S. Sidhu, Science 2013, 339, 590-595.
M. Gorelik, S. Orlicky, M. A. Sartori, X. Tang, E. Marcon, I. Kurinov, J. F. Greenblatt, M. Tyers, J. Moffat, F. Sicheri, S. S. Sidhu, Proc. Natl. Acad. Sci. USA 2016, 113, 3527-3532.
M. Gorelik, N. Manczyk, A. Pavlenco, I. Kurinov, S. S. Sidhu, F. Sicheri, Structure 2018, 26, 1226-1236.e3.
A. Hoffmann, M. Kovermann, H. Lilie, M. Fiedler, J. Balbach, R. Rudolph, S. Pfeifer, PLoS One 2012, 7, e31298.
M. D. Canny, N. Moatti, L. C. K. Wan, A. Fradet-Turcotte, D. Krasner, P. A. Mateos-Gomez, M. Zimmermann, A. Orthwein, Y.-C. Juang, W. Zhang, S. M. Noordermeer, E. Seclen, M. D. Wilson, A. Vorobyov, M. Munro, A. Ernst, T. F. Ng, T. Cho, P. M. Cannon, S. S. Sidhu, F. Sicheri, D. Durocher, Nat. Biotechnol. 2018, 36, 95-102.
S. Lorey, E. Fiedler, A. Kunert, J. Nerkamp, C. Lange, M. Fiedler, E. Bosse-Doenecke, M. Meysing, M. Gloser, C. Rundfeldt, U. Rauchhaus, I. Hänssgen, T. Göttler, A. Steuernagel, U. Fiedler, U. Haupts, J. Biol. Chem. 2014, 289, 8493-8507.
I. Leung, N. Jarvik, S. S. Sidhu, J. Mol. Biol. 2017, 429, 115-127.
K. Takada, H. Nasu, N. Hibi, Y. Tsukada, T. Shibasaki, K. Fujise, M. Fujimuro, H. Sawada, H. Yokosawa, K. Ohkawa, Clin. Chem. 1997, 43, 1188-1195.
M. Majetschak, S. M. Cohn, U. Obertacke, K. G. Proctor, J. Trauma Inj. Infect. Crit. Care 2004, 56, 991-1000.
K. Huynh, C. L. Partch, Curr. Protoc. Protein Sci. 2015, 79, 28.9.1-28.9.14.
W. Miao, K. Sakai, H. Sato, R. Imamura, N. Jangphattananont, J. Takagi, M. Nishita, Y. Minami, K. Matsumoto, Cancer Sci. 2019, 110, 3340-3349.