The structural influence of the oncogenic driver mutation N642H in the STAT5B SH2 domain.

ABSTRACT: The point mutation N642H of the signal transducer and activator of transcription 5B (STAT5B) protein is associated with aggressive and drug-resistant forms of leukemia. This mutation is thought to promote cancer due to hyperactivation of STAT5B caused by increased stability of the active, parallel dimer state. However, the molecular mechanism leading to this stabilization is not well understood as there is currently no structure of the parallel dimer. To investigate the mutation's mechanism of action, we conducted extensive all-atom molecular dynamics simulations of multiple oligomeric forms of both STAT5B and STAT5B^N642H, including a model for the parallel dimer. The N642H mutation directly affects the hydrogen bonding network within the phosphotyrosine (pY)-binding pocket of t

SUBMITTER: Haas-Neill L 

PROVIDER: S-EPMC11670306 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature