Adaptor proteins play a pivotal role in cellular signaling mediating a multitude of protein-protein interaction critical for cellular homeostasis. Dysregulation of these interactions has been linked to the onset of various cancer pathologies and exploited by viral pathogens during host cell takeover. CrkL is an adaptor protein composed of an N-terminal SH2 domain followed by two SH3 domains that mediate interactions with diverse partners through the recognition of specific binding motifs. In this study, we employed proteomic peptide-phage display (ProP-PD) to comprehensively explore the short linear motif (SLiM)-based interactions of CrkL. Furthermore, we scrutinized how the binding affinity for selected peptides was influenced in the context of the full-length CrkL versus the isolated N-SH3 domain. Importantly, our results provided insights into SLiM-binding sites within previously reported interactors, as well as revealing novel human and viral ligands, expanding our understanding of the interactions mediated by CrkL and highlighting the significance of SLiM-based interactions in mediating adaptor protein function, with implications for cancer and viral pathologies.

Exploring the short linear motif-mediated protein-protein interactions of CrkL through ProP-PD / Pagano, L.; Simonetti, L.; Pennacchietti, V.; Toto, A.; Malagrinò, F.; Ivarsson, Y.; Gianni, S.. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - 703:(2024), p. 149658. [10.1016/j.bbrc.2024.149658]

Exploring the short linear motif-mediated protein-protein interactions of CrkL through ProP-PD

Pagano, L.;Pennacchietti, V.;Toto, A.;Gianni, S.
2024

Abstract

Adaptor proteins play a pivotal role in cellular signaling mediating a multitude of protein-protein interaction critical for cellular homeostasis. Dysregulation of these interactions has been linked to the onset of various cancer pathologies and exploited by viral pathogens during host cell takeover. CrkL is an adaptor protein composed of an N-terminal SH2 domain followed by two SH3 domains that mediate interactions with diverse partners through the recognition of specific binding motifs. In this study, we employed proteomic peptide-phage display (ProP-PD) to comprehensively explore the short linear motif (SLiM)-based interactions of CrkL. Furthermore, we scrutinized how the binding affinity for selected peptides was influenced in the context of the full-length CrkL versus the isolated N-SH3 domain. Importantly, our results provided insights into SLiM-binding sites within previously reported interactors, as well as revealing novel human and viral ligands, expanding our understanding of the interactions mediated by CrkL and highlighting the significance of SLiM-based interactions in mediating adaptor protein function, with implications for cancer and viral pathologies.
2024
Phage display; SH3 domain; short linear motif
01 Pubblicazione su rivista::01a Articolo in rivista
Exploring the short linear motif-mediated protein-protein interactions of CrkL through ProP-PD / Pagano, L.; Simonetti, L.; Pennacchietti, V.; Toto, A.; Malagrinò, F.; Ivarsson, Y.; Gianni, S.. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - 703:(2024), p. 149658. [10.1016/j.bbrc.2024.149658]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1702558
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