Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387234080> ?p ?o ?g. }
- W4387234080 abstract "Abstract Short Linear Motifs (SLiMs) are pivotal in mediating interactions between intrinsically disordered proteins and their binding partners. SLiMs exhibit sequence degeneracy and undergo regulation by post-translational modifications, including phosphorylation. These modifications can either augment or attenuate the binding affinities for a SliM and its binding partner. In this study, we set out to integrate biomolecular simulations, in silico high-throughput mutational scans, and biophysical measurements to elucidate the structural details of phospho-regulation in a class of SLiMs crucial for autophagy, known as LC3 interacting regions (LIRs). As a case study, we investigated the interaction between optineurin and LC3B, a system extensively characterized by experiments. We confirmed the robustness of our computational approach through the comparison with the available experimental data. Furthermore, we unveiled the previously unexplored role of the N-terminal flanking region upstream of the LIR core motif. Our study offers an atom-level perspective on the structural mechanisms and conformational alterations induced by phosphorylation in optineurin and LC3B recognition. Additionally, we assessed the impact of disease-related mutations on optineurin, accounting for different functional features. Notably, we established an approach based on Microfluidic Diffusional Sizing to investigate the binding affinity of SLiMs to target proteins, enabling precise measurements of the dissociation constant for a selection of variants from the in silico mutational screening. Overall, our work provides a versatile toolkit to characterize other LIR-containing proteins and their modulation by phosphorylation or other phospho-regulated SLiMs, thereby advancing the understanding of important cellular processes." @default.
- W4387234080 created "2023-10-02" @default.
- W4387234080 creator A5001357391 @default.
- W4387234080 creator A5034972106 @default.
- W4387234080 creator A5060221943 @default.
- W4387234080 creator A5061312008 @default.
- W4387234080 creator A5086079835 @default.
- W4387234080 creator A5089976447 @default.
- W4387234080 creator A5070728908 @default.
- W4387234080 date "2023-09-30" @default.
- W4387234080 modified "2023-10-09" @default.
- W4387234080 title "Phosphorylation-induced rewiring of intermolecular interactions with LC3B: local and long-range effects on short linear motifs" @default.
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