Grb2 Y160F mutant mimics the wild-type monomeric state dynamics and the monomer-dimer equilibrium
The Growth factor receptor-bound protein 2 (Grb2) participates in early signaling complexes and regulates tyrosine kinase-mediated signal transduction through a monomer-dimer equilibrium. Grb2 dimeric state inhibits signal transduction whereas the monomer promotes signaling downstream. Since Grb2 di...
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | Brasil |
| Institución: | Universidade Estadual Paulista (UNESP) |
| Repositorio: | Repositório Institucional da UNESP |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unesp.br:11449/303148 |
| Acceso en línea: | http://dx.doi.org/10.1016/j.ijbiomac.2024.134945 https://hdl.handle.net/11449/303148 |
| Access Level: | acceso abierto |
| Palabra clave: | Grb2 monomer Grb2 Y160F Monomer-dimer equilibrium |
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Grb2 Y160F mutant mimics the wild-type monomeric state dynamics and the monomer-dimer equilibriumGrb2 monomerGrb2 Y160FMonomer-dimer equilibriumThe Growth factor receptor-bound protein 2 (Grb2) participates in early signaling complexes and regulates tyrosine kinase-mediated signal transduction through a monomer-dimer equilibrium. Grb2 dimeric state inhibits signal transduction whereas the monomer promotes signaling downstream. Since Grb2 dimer KD is ∼0.8 μM, studies focused on the monomer are still challenging and require mutations or interaction with phosphotyrosine peptides. However, these mutants were never characterized considering their effects on protein structure and dynamics in solution. Here, we present the biophysical characterization of Grb2Y160F, the first Grb2 mutant to induce protein monomerization without disrupting its native behavior in solution due to net charge modifications or interaction with peptides. We also identified that Grb2Y160F exists in a monomer-dimer equilibrium. Grb2Y160F ability to dimerize implies that different dimerization interfaces might regulate signaling pathways in distinct ways and raises an important question about the role of the Y160 residue in other dimerization interfaces.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Department of Physics São Paulo State University (UNESP) Institute of Biosciences Humanities and Exact Sciences, Sao Jose do Rio Preto, SPMultiuser Center for Biomolecular Innovation (CMIB) São Paulo State University (UNESP) Institute of Biosciences Humanities and Exact Sciences, Sao Jose do Rio Preto, SPBiophysics Institute Carlos Chagas Filho Federal University of Rio de Janeiro, RJApplied Physics Department Institute of Physics University of São Paulo (USP), SPDepartment of Physics São Paulo State University (UNESP) Institute of Biosciences Humanities and Exact Sciences, Sao Jose do Rio Preto, SPMultiuser Center for Biomolecular Innovation (CMIB) São Paulo State University (UNESP) Institute of Biosciences Humanities and Exact Sciences, Sao Jose do Rio Preto, SPFAPESP: 2019/24974-0FAPESP: 2022/00347-0FAPESP: 2023/01632-2FAPESP: 2023/01744-5FAPESP: 2023/09642-7CNPq: 409272/2021-3CAPES: 88882.434373/2019-01CAPES: 88887.509994/2020-00CAPES: 88887.643249/2021-00CAPES: 88887.799480/2022-00Universidade Estadual Paulista (UNESP)Federal University of Rio de JaneiroUniversidade de São Paulo (USP)2025-04-29T19:28:44Z2024-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.ijbiomac.2024.134945International Journal of Biological Macromolecules, v. 279.1879-00030141-8130https://hdl.handle.net/11449/30314810.1016/j.ijbiomac.2024.1349452-s2.0-85202566902Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Biological Macromoleculesinfo:eu-repo/semantics/openAccessCasteluci, G. [UNESP]Dias, R. V.R. [UNESP]Martins, I. B.S. [UNESP]Fernandes, R. A.Tedesco, J. A. [UNESP]Caruso, I. P. [UNESP]de Araujo, A. S. [UNESP]Itri, R.Melo, F. A. [UNESP]2025-04-30T14:29:15Zoai:repositorio.unesp.br:11449/303148Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462025-04-30T14:29:15Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
| dc.title.none.fl_str_mv |
Grb2 Y160F mutant mimics the wild-type monomeric state dynamics and the monomer-dimer equilibrium |
| title |
Grb2 Y160F mutant mimics the wild-type monomeric state dynamics and the monomer-dimer equilibrium |
| spellingShingle |
Grb2 Y160F mutant mimics the wild-type monomeric state dynamics and the monomer-dimer equilibrium Casteluci, G. [UNESP] Grb2 monomer Grb2 Y160F Monomer-dimer equilibrium |
| title_short |
Grb2 Y160F mutant mimics the wild-type monomeric state dynamics and the monomer-dimer equilibrium |
| title_full |
Grb2 Y160F mutant mimics the wild-type monomeric state dynamics and the monomer-dimer equilibrium |
| title_fullStr |
Grb2 Y160F mutant mimics the wild-type monomeric state dynamics and the monomer-dimer equilibrium |
| title_full_unstemmed |
Grb2 Y160F mutant mimics the wild-type monomeric state dynamics and the monomer-dimer equilibrium |
| title_sort |
Grb2 Y160F mutant mimics the wild-type monomeric state dynamics and the monomer-dimer equilibrium |
| dc.creator.none.fl_str_mv |
Casteluci, G. [UNESP] Dias, R. V.R. [UNESP] Martins, I. B.S. [UNESP] Fernandes, R. A. Tedesco, J. A. [UNESP] Caruso, I. P. [UNESP] de Araujo, A. S. [UNESP] Itri, R. Melo, F. A. [UNESP] |
| author |
Casteluci, G. [UNESP] |
| author_facet |
Casteluci, G. [UNESP] Dias, R. V.R. [UNESP] Martins, I. B.S. [UNESP] Fernandes, R. A. Tedesco, J. A. [UNESP] Caruso, I. P. [UNESP] de Araujo, A. S. [UNESP] Itri, R. Melo, F. A. [UNESP] |
| author_role |
author |
| author2 |
Dias, R. V.R. [UNESP] Martins, I. B.S. [UNESP] Fernandes, R. A. Tedesco, J. A. [UNESP] Caruso, I. P. [UNESP] de Araujo, A. S. [UNESP] Itri, R. Melo, F. A. [UNESP] |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) Federal University of Rio de Janeiro Universidade de São Paulo (USP) |
| dc.subject.por.fl_str_mv |
Grb2 monomer Grb2 Y160F Monomer-dimer equilibrium |
| topic |
Grb2 monomer Grb2 Y160F Monomer-dimer equilibrium |
| description |
The Growth factor receptor-bound protein 2 (Grb2) participates in early signaling complexes and regulates tyrosine kinase-mediated signal transduction through a monomer-dimer equilibrium. Grb2 dimeric state inhibits signal transduction whereas the monomer promotes signaling downstream. Since Grb2 dimer KD is ∼0.8 μM, studies focused on the monomer are still challenging and require mutations or interaction with phosphotyrosine peptides. However, these mutants were never characterized considering their effects on protein structure and dynamics in solution. Here, we present the biophysical characterization of Grb2Y160F, the first Grb2 mutant to induce protein monomerization without disrupting its native behavior in solution due to net charge modifications or interaction with peptides. We also identified that Grb2Y160F exists in a monomer-dimer equilibrium. Grb2Y160F ability to dimerize implies that different dimerization interfaces might regulate signaling pathways in distinct ways and raises an important question about the role of the Y160 residue in other dimerization interfaces. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024-11-01 2025-04-29T19:28:44Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.ijbiomac.2024.134945 International Journal of Biological Macromolecules, v. 279. 1879-0003 0141-8130 https://hdl.handle.net/11449/303148 10.1016/j.ijbiomac.2024.134945 2-s2.0-85202566902 |
| url |
http://dx.doi.org/10.1016/j.ijbiomac.2024.134945 https://hdl.handle.net/11449/303148 |
| identifier_str_mv |
International Journal of Biological Macromolecules, v. 279. 1879-0003 0141-8130 10.1016/j.ijbiomac.2024.134945 2-s2.0-85202566902 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
International Journal of Biological Macromolecules |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
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Universidade Estadual Paulista (UNESP) |
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UNESP |
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UNESP |
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Repositório Institucional da UNESP |
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Repositório Institucional da UNESP |
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Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
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repositoriounesp@unesp.br |
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