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Open AccessArticle

Understanding the Mechanism of Recognition of Gab2 by the N-SH2 Domain of SHP2

Istituto Pasteur—Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche “A. Rossi Fanelli” and Istituto di Biologia e Patologia Molecolari del CNR, Sapienza Università di Roma, 00185 Rome, Italy
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Author to whom correspondence should be addressed.
Authors contributed equally to this work.
Life 2020, 10(6), 85; https://doi.org/10.3390/life10060085
Received: 28 May 2020 / Revised: 8 June 2020 / Accepted: 8 June 2020 / Published: 11 June 2020
Gab2 is a scaffold protein with a crucial role in colocalizing signaling proteins and it is involved in the regulation of several important molecular pathways. SHP2 is a protein phosphatase that binds, through its two SH2 domains, specific consensus sequences presenting a phosphorylated tyrosine located on the disordered tail of Gab2. To shed light on the details of such a fundamental interaction for the physiology of the cell, we present a complete mutational analysis of the kinetics of binding between the N-SH2 domain of SHP2 and a peptide mimicking a specific region of Gab2. By analyzing kinetic data, we determined structural features of the transition state of the N-SH2 domain binding to Gab2, highlighting a remarkable cooperativity of the binding reaction. Furthermore, comparison of these data with ones previously obtained for another SH2 domain suggests the presence of underlying general features characterizing the binding process of SH2 domains. Data are discussed under the light of previous works on SH2 domains. View Full-Text
Keywords: binding kinetics; intrinsically disordered protein; mutagenesis binding kinetics; intrinsically disordered protein; mutagenesis
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Visconti, L.; Malagrinò, F.; Pagano, L.; Toto, A. Understanding the Mechanism of Recognition of Gab2 by the N-SH2 Domain of SHP2. Life 2020, 10, 85.

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