Fig. 2: PP1C binds SHOC2 predominantly via complementary electrostatic interactions, whereas MRAS binds SHOC2 via its switch I and II regions.
From: Structural basis for SHOC2 modulation of RAS signalling
a, Electrostatic surfaces of SHOC2 and PP1C create a complementary binding interface between acidic (red) and basic (blue) patches. MRAS is omitted for clarity. b, MRAS(GCP) (salmon) interacts with SHOC2 (green) via its switch I and II regions (dark red). Alignment of the switch I and II regions of GDP-bound KRAS (PDB: 4OBE) (yellow) showing selected sidechains (spheres), reveals steric clashes with SHOC2. PP1C is omitted for clarity. c, Detailed view of MRAS(GCP) switch I (salmon, top) and switch II (salmon, bottom) interactions with SHOC2 (green), with key hydrogen bonds and π-stacking interactions shown as dashed lines. d, RAS (salmon) with SHOC2 (green) and PP1C (purple) binding interfaces highlighted (left), which have considerable overlap with the RAF RBD–CRD binding surface (yellow, right).
