Fig. 7
From: Structural and functional consequences of the STAT5BN642H driver mutation
STAT5B and STAT5BN642H dimer interfaces and flexibility of the SH2 ___domain. a The number of contacts formed between the monomers in the unphosphorylated anti-parallel dimeric structures of STAT5B (top) and STAT5BN642H (bottom) as a function of simulation time. The three curves correspond to three independent simulations. Contacts are defined if any two atoms are within 6 Å; moving average over every 5 ns is plotted. b The structures of the STAT5B (system 3) at 75 ns depicting dimer dissociation (top) and STAT5BN642H (system 1) at the end of 1 µs simulation (bottom). The color scheme in b corresponds to the individual domains: CCD, cyan; DBD, blue; linker ___domain, purple; SH2 ___domain, orange. Residue 642 is highlighted in green. c Inter-chain contacts formed over the 1 µs simulation, shown by the atom pairs within a minimum inter-atomic distance within a 6 Å cutoff. The boundaries of the individual domains are shown for clarity, and the two dimer interfaces are highlighted in gray boxes. d Sustained inter-chain contacts formed over the 1 µs simulation. The bottom panel demonstrates the hot-spot residues in licorice representation (chain A, left; chain B, right). See the simulation methods for the definition of the inter-chain contacts. Dynamic light scattering experiments in e show that STAT5BN642H (50 µM) adopts a more closely packed dimer compared to STAT5B (50 µM). The values for diameter are reported ± SD as the average of three independent runs. f Root mean square fluctuation (RMSF) of the α-carbon atoms of the SH2 ___domain in STAT5B monomer and STAT5BN642H dimer. The shading indicates statistical uncertainty. Source data are provided as a Source Data file
