Allosteric Coupling in Full-Length Lyn Kinase Revealed by Molecular Dynamics and Network Analysis.

ABSTRACT: Lyn is a multifunctional Src-family kinase (SFK) that regulates immune signaling and has been implicated in diverse types of cancer. Unlike other SFKs, its full-length structure and regulatory dynamics remain poorly characterized. In this study, we present the first long-timescale molecular dynamics analysis of full-length Lyn, including the SH3, SH2, and SH1 domains, across wildtype, ligand-bound, and cancer-associated mutant states. Using principal component analysis, dynamic cross-correlation matrices, and network-based methods, we show that ATP binding stabilizes the kinase core and promotes interdomain coordination, while the ATP-competitive inhibitor dasatinib and specific mutations (e.g., E290K, I364N) induce conformational decoupling and weaken long-range communication. We identify

SUBMITTER: Rabipour M 

PROVIDER: S-EPMC12192854 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature