| Full text | |
| Author(s): |
Casteluci, G.
;
Dias, R. V. R.
;
Martins, I. B. S.
;
Fernandes, R. A.
;
Tedesco, J. A.
;
Caruso, I. P.
;
de Araujo, A. S.
;
Itri, R.
;
Melo, F. A.
Total Authors: 9
|
| Document type: | Journal article |
| Source: | International Journal of Biological Macromolecules; v. 279, p. 9-pg., 2024-08-30. |
| Abstract | |
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 similar to 0.8 mu M, 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 Grb2Y(160F), 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 Grb2Y(160F) exists in a monomer-dimer equilibrium. Grb2(Y160F) 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. (AU) | |
| FAPESP's process: | 22/00347-0 - Attacking dengue on two fronts: using computer simulations to develop new antiviral compounds and vaccines |
| Grantee: | Alexandre Suman de Araujo |
| Support Opportunities: | Scholarships abroad - Research |
| FAPESP's process: | 16/13884-2 - Multi-User Equipment approved in grant 2013/07600-3: MicroScale Thermophoresis (MST) |
| Grantee: | Glaucius Oliva |
| Support Opportunities: | Multi-user Equipment Program |
| FAPESP's process: | 23/09642-7 - Characterization of conformational changes in the globular domain of the M2-1 protein of hRSV and hMPV: mechanisms involving open-closed equilibrium and implications. |
| Grantee: | Raphael Vinicius Rodrigues Dias |
| Support Opportunities: | Scholarships in Brazil - Support Program for Fixating Young Doctors |
| FAPESP's process: | 19/24974-0 - Function studies of Grb2 through nuclear magnetic resonance and fluorescence: correlating dynamics and structure |
| Grantee: | Fernando Alves de Melo |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 23/01632-2 - Characterization of conformational changes in the globular domain of the M2-1 protein of hRSV and hMPV: mechanisms involving open-closed equilibrium and implications |
| Grantee: | Ícaro Putinhon Caruso |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 23/01744-5 - Correlation between the structure and dynamics of GRB2 protein and its folding excited states |
| Grantee: | Fernando Alves de Melo |
| Support Opportunities: | Regular Research Grants |