| Full text | |
| Author(s): |
Sanches, Karoline
[1]
;
Caruso, Icaro P.
[2, 1, 3]
;
Almeida, Fabio C. L.
[2, 3]
;
Melo, Fernando A.
[1]
Total Authors: 4
|
| Affiliation: | [1] Sao Paulo State Univ UNESP, Dept Phys, Multiuser Ctr Biomol Innovat CMIB, Sao Jose Do Rio Preto, SP - Brazil
[2] Univ Fed Rio de Janeiro, Inst Med Biochem IBqM, Rio De Janeiro - Brazil
[3] Univ Fed Rio de Janeiro, Natl Ctr Struct Biol & Bioimaging CENABIO, Natl Ctr Nucl Magnet Resonance CNRMN, Rio De Janeiro - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | SCIENTIFIC REPORTS; v. 10, n. 1 AUG 3 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
The growth factor receptor-bound protein 2 (Grb2) is a key factor in the regulation of cell survival, proliferation, differentiation, and metabolism. In its structure, the central Src homology 2 (SH2) domain is flanked by two Src homology 3 (SH3). SH2 is the most important domain in the recognition of phosphotyrosines. Here, we present the first dynamical characterization of Grb2-SH2 domain in the free state and in the presence of phosphopeptide EpYINSQV at multiple timescales, which revealed valuable information to the understanding of phophotyrosine sensing mechanism. Grb2-SH2 presented two dynamically independent subdomains, subdomain I involved in pY recognition and subdomain II is the pY+2 specificity pocket. Under semi-saturated concentrations of pY-pep we observed fuzzy interactions, which led to chemical exchange observed by NMR. This information was used to describe the encounter complex. The association with pY-pep is dynamic, involving fuzzy interactions and multiple conformations of pY-pep with negative and hydrophobic residues, creating an electrostatic-potential that drives the binding of pY-pep. The recognition face is wider than the binding site, with many residues beyond the central SH2 binding site participating in the association complex, which contribute to explain previously reported capability of Grb2 to recognize remote pY. (AU) | |
| FAPESP's process: | 14/17630-0 - Functional studies of tyrosine kinase fibroblast growth factor receptor (FGFR2), the adapter growth factor receptor-Bound protein 2 (Grb2) and tyrosine phosphatase SHP2 |
| Grantee: | Fernando Alves de Melo |
| Support Opportunities: | Regular Research Grants |