Ligand Binding to the Membrane-Distal Domain of the Met Receptor Induces Dimerization at the Membrane-Proximal Domain
Activation of cytokine and growth factor receptors by ligands triggers crucial cellular responses in various physiological processes. However, our understanding of their structural basis remains incomplete due to the limited information on the active ligand–receptor complex structure. Their structur...
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2025
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| _version_ | 1849927623817297920 |
|---|---|
| author | Neval Yilmaz (1544557) |
| author2 | Hiroki Tanino (22686882) Shun Sakuraba (1368381) Romain Amyot (9657017) Holger Flechsig (213426) Atsushi Matsumoto (593817) Hidetoshi Kono (19475) Leonardo Puppulin (11688279) Mikihiro Shibata (2075461) Hiroshi Aoyama (832169) Tsuyoshi Inoue (559318) Kunio Matsumoto (412408) Katsuya Sakai (11688282) |
| author2_role | author author author author author author author author author author author author |
| author_facet | Neval Yilmaz (1544557) Hiroki Tanino (22686882) Shun Sakuraba (1368381) Romain Amyot (9657017) Holger Flechsig (213426) Atsushi Matsumoto (593817) Hidetoshi Kono (19475) Leonardo Puppulin (11688279) Mikihiro Shibata (2075461) Hiroshi Aoyama (832169) Tsuyoshi Inoue (559318) Kunio Matsumoto (412408) Katsuya Sakai (11688282) |
| author_role | author |
| dc.creator.none.fl_str_mv | Neval Yilmaz (1544557) Hiroki Tanino (22686882) Shun Sakuraba (1368381) Romain Amyot (9657017) Holger Flechsig (213426) Atsushi Matsumoto (593817) Hidetoshi Kono (19475) Leonardo Puppulin (11688279) Mikihiro Shibata (2075461) Hiroshi Aoyama (832169) Tsuyoshi Inoue (559318) Kunio Matsumoto (412408) Katsuya Sakai (11688282) |
| dc.date.none.fl_str_mv | 2025-11-26T06:07:17Z |
| dc.identifier.none.fl_str_mv | 10.1021/acsnano.4c17358.s005 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/media/Ligand_Binding_to_the_Membrane-Distal_Domain_of_the_Met_Receptor_Induces_Dimerization_at_the_Membrane-Proximal_Domain/30718137 |
| dc.rights.none.fl_str_mv | CC BY-NC 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biophysics Biochemistry Cell Biology Molecular Biology Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified molecular dynamics simulations luciferase complementary assay hepatocyte growth factor growth factor receptors electron microscopy experiments chemically fixing prior also conducted split various physiological processes proximal domain activation proximal region sema domain ipt4 domain distal domain physiological hgf structural features resolution characterization protein level living cells limited information induced dimerization active complex |
| dc.title.none.fl_str_mv | Ligand Binding to the Membrane-Distal Domain of the Met Receptor Induces Dimerization at the Membrane-Proximal Domain |
| dc.type.none.fl_str_mv | Dataset Media info:eu-repo/semantics/publishedVersion dataset |
| description | Activation of cytokine and growth factor receptors by ligands triggers crucial cellular responses in various physiological processes. However, our understanding of their structural basis remains incomplete due to the limited information on the active ligand–receptor complex structure. Their structural analysis poses two significant challenges: preserving the complex structure during isolation from living cells and achieving high-resolution characterization. In this study, we analyzed the structure of the active complex of the hepatocyte growth factor (HGF)-Met receptor by chemically fixing prior to isolating from living cells and high-speed atomic force microscopy imaging at the single-protein level. We also conducted split-luciferase complementary assay and cryo-electron microscopy experiments for the HGF-Met extracellular domain complex and complemented these results with molecular dynamics simulations. We found that HGF binding to the Sema domain of Met promotes homotypic dimerization at the membrane-proximal region of Met, specifically the IPT4 domain. In summary, our study unveils the structural features of the physiological HGF-Met complex and clarifies the ligand-induced dimerization of the Met receptor. |
| eu_rights_str_mv | openAccess |
| id | Manara_5ce5b63fdf48c5367a22f1633b7410b9 |
| identifier_str_mv | 10.1021/acsnano.4c17358.s005 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30718137 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY-NC 4.0 |
| spelling | Ligand Binding to the Membrane-Distal Domain of the Met Receptor Induces Dimerization at the Membrane-Proximal DomainNeval Yilmaz (1544557)Hiroki Tanino (22686882)Shun Sakuraba (1368381)Romain Amyot (9657017)Holger Flechsig (213426)Atsushi Matsumoto (593817)Hidetoshi Kono (19475)Leonardo Puppulin (11688279)Mikihiro Shibata (2075461)Hiroshi Aoyama (832169)Tsuyoshi Inoue (559318)Kunio Matsumoto (412408)Katsuya Sakai (11688282)BiophysicsBiochemistryCell BiologyMolecular BiologyBiological Sciences not elsewhere classifiedChemical Sciences not elsewhere classifiedmolecular dynamics simulationsluciferase complementary assayhepatocyte growth factorgrowth factor receptorselectron microscopy experimentschemically fixing prioralso conducted splitvarious physiological processesproximal domain activationproximal regionsema domainipt4 domaindistal domainphysiological hgfstructural featuresresolution characterizationprotein levelliving cellslimited informationinduced dimerizationactive complexActivation of cytokine and growth factor receptors by ligands triggers crucial cellular responses in various physiological processes. However, our understanding of their structural basis remains incomplete due to the limited information on the active ligand–receptor complex structure. Their structural analysis poses two significant challenges: preserving the complex structure during isolation from living cells and achieving high-resolution characterization. In this study, we analyzed the structure of the active complex of the hepatocyte growth factor (HGF)-Met receptor by chemically fixing prior to isolating from living cells and high-speed atomic force microscopy imaging at the single-protein level. We also conducted split-luciferase complementary assay and cryo-electron microscopy experiments for the HGF-Met extracellular domain complex and complemented these results with molecular dynamics simulations. We found that HGF binding to the Sema domain of Met promotes homotypic dimerization at the membrane-proximal region of Met, specifically the IPT4 domain. In summary, our study unveils the structural features of the physiological HGF-Met complex and clarifies the ligand-induced dimerization of the Met receptor.2025-11-26T06:07:17ZDatasetMediainfo:eu-repo/semantics/publishedVersiondataset10.1021/acsnano.4c17358.s005https://figshare.com/articles/media/Ligand_Binding_to_the_Membrane-Distal_Domain_of_the_Met_Receptor_Induces_Dimerization_at_the_Membrane-Proximal_Domain/30718137CC BY-NC 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/307181372025-11-26T06:07:17Z |
| spellingShingle | Ligand Binding to the Membrane-Distal Domain of the Met Receptor Induces Dimerization at the Membrane-Proximal Domain Neval Yilmaz (1544557) Biophysics Biochemistry Cell Biology Molecular Biology Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified molecular dynamics simulations luciferase complementary assay hepatocyte growth factor growth factor receptors electron microscopy experiments chemically fixing prior also conducted split various physiological processes proximal domain activation proximal region sema domain ipt4 domain distal domain physiological hgf structural features resolution characterization protein level living cells limited information induced dimerization active complex |
| status_str | publishedVersion |
| title | Ligand Binding to the Membrane-Distal Domain of the Met Receptor Induces Dimerization at the Membrane-Proximal Domain |
| title_full | Ligand Binding to the Membrane-Distal Domain of the Met Receptor Induces Dimerization at the Membrane-Proximal Domain |
| title_fullStr | Ligand Binding to the Membrane-Distal Domain of the Met Receptor Induces Dimerization at the Membrane-Proximal Domain |
| title_full_unstemmed | Ligand Binding to the Membrane-Distal Domain of the Met Receptor Induces Dimerization at the Membrane-Proximal Domain |
| title_short | Ligand Binding to the Membrane-Distal Domain of the Met Receptor Induces Dimerization at the Membrane-Proximal Domain |
| title_sort | Ligand Binding to the Membrane-Distal Domain of the Met Receptor Induces Dimerization at the Membrane-Proximal Domain |
| topic | Biophysics Biochemistry Cell Biology Molecular Biology Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified molecular dynamics simulations luciferase complementary assay hepatocyte growth factor growth factor receptors electron microscopy experiments chemically fixing prior also conducted split various physiological processes proximal domain activation proximal region sema domain ipt4 domain distal domain physiological hgf structural features resolution characterization protein level living cells limited information induced dimerization active complex |