Decoding phospho-regulation and flanking regions in autophagy-associated short linear motifs.

ABSTRACT: Short Linear Motifs (SLiMs) play a pivotal role in the interactions between intrinsically disordered proteins and their binding partners. SLiMs can undergo regulation through post-translational modifications, including phosphorylation. The flanking regions surrounding the core motifs also exert a crucial role for the interaction. While phosphorylation and flanking regions are known to influence SLiM function, the mechanistic basis of this regulation remains poorly understood. We integrate biomolecular simulations, in silico high-throughput mutational scans, and biophysical experiments to elucidate the phospho-regulation in SLiMs crucial for autophagy, i.e., the LC3 interacting regions (LIRs). We investigate the Optineurin LIR, which perfectly exemplifies a class of LIR with a complex inter

SUBMITTER: Utichi M 

PROVIDER: S-EPMC12368060 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature