SH2 Domains: Folding, Binding and Therapeutical Approaches

Autor: Awa Diop, Daniele Santorelli, Francesca Malagrinò, Caterina Nardella, Valeria Pennacchietti, Livia Pagano, Lucia Marcocci, Paola Pietrangeli, Stefano Gianni, Angelo Toto
Přispěvatelé: Awa, Diop, Daniele, Santorelli, Malagrino', Francesca, Caterina, Nardella, Valeria, Pennacchietti, Livia, Pagano, Lucia, Marcocci, Paola, Pietrangeli, Stefano, Gianni, Angelo, Toto
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences
ISSN: 1422-0067
DOI: 10.3390/ijms232415944
Popis: SH2 (Src Homology 2) domains are among the best characterized and most studied protein-protein interaction (PPIs) modules able to bind and recognize sequences presenting a phosphorylated tyrosine. This post-translational modification is a key regulator of a plethora of physiological and molecular pathways in the eukaryotic cell, so SH2 domains possess a fundamental role in cell signaling. Consequently, several pathologies arise from the dysregulation of such SH2-domains mediated PPIs. In this review, we recapitulate the current knowledge about the structural, folding stability, and binding properties of SH2 domains and their roles in molecular pathways and pathogenesis. Moreover, we focus attention on the different strategies employed to modulate/inhibit SH2 domains binding. Altogether, the information gathered points to evidence that pharmacological interest in SH2 domains is highly strategic to developing new therapeutics. Moreover, a deeper understanding of the molecular determinants of the thermodynamic stability as well as of the binding properties of SH2 domains appears to be fundamental in order to improve the possibility of preventing their dysregulated interactions.
Databáze: OpenAIRE
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