Fig. 3: Membrane anchoring of PUMA and BCL-xL constrains orientation of the BH3-in-groove interface towards the lipid membrane.

a Representative snapshots from the supplementary Movies 1 and 2 illustrating the results of molecular dynamics simulations over time performed to study the behavior of BCL-xL complexes interacting with PUMABH3 or dNPUMA. Phosphatidyl choline headgroups are represented in van der Waals representation and lipid tails are displayed in blue lines to provide a clear view of TA. The helical structure of TA is depicted in Cartoon representation. The simulations were carried out for 2 μs. At t = 0, the initial orientations of the PUMABH3/BCL-xL and dNPUMA/BCL-xL complexes are depicted. During the simulation, the PUMABH3/BCL-xL globular part moves away from the membrane, while this phenomenon was less pronounced for the dNPUMA/BCL-xL complex. b Dynamics of the globular part of the PUMABH3/BCL-xL and dNPUMA/BCL-xL complexes relative to the membrane over a 2000 ns timespan. BCL-xL tilt was defined as the angle between the BCL-xL α5 helix and the membrane plane (left panel). BCL-xL roll was defined as the angle between a plane formed by BCL-xL α5 and α6 helices and the membrane plane (right panel).