Intrinsic Disorder in PTEN and its Interactome Confers Structural Plasticity and Functional Versatility

摘要: IDPs, while structurally poor, are functionally rich by virtue of their flexibility and modularity. However, how mutations in IDPs elicit diseases, remain elusive. Herein, we have identified tumor suppressor PTEN as an intrinsically disordered protein (IDP) elucidated the molecular principles which its region (IDR) at carboxyl-terminus (C-tail) executes functions. Post-translational modifications, conserved eukaryotic linear motifs recognition features present C-tail IDR enhance PTEN's protein-protein interactions that required for myriad cellular primary secondary interactomes also enriched most being cancer related, revealing functions emanate from nucleated IDR, form pliable network-hubs. Together, higher order functional networks operate via multiple IDP-IDP facilitated IDR. Targeting interaction hubs emerges a new paradigm treatment related pathologies.