“…Structural studies have been conducted for CCM2 and CCM3 that discovered novel domains in both proteins (Fisher et al, 2013; Li et al, 2010), and the structural basis for CCM2 and CCM3 interactions with binding partners (Draheim et al, 2015; Fisher et al, 2015b; Li et al, 2011; Xu et al, 2013; Zhang et al, 2013). Similarly, structural studies have been conducted for KRIT1, and have facilitated the discovery of a Nudix fold domain at the KRIT1 N-terminus (Liu et al, 2013), a novel PTB-binding site which interacts with the protein ICAP1 (integrin cytoplasmic associated protein 1) (Liu and Boggon, 2013; Liu et al, 2013), the mode of interactions with CCM2 (Fisher et al, 2015a) and (SNX17) sorting nexin 17 (Stiegler et al, 2014), and the distinct and unusual manner by which the C-terminal FERM (band 4-point-1, ezrin, radixin, moesin) domain binds to the small GTPase Rap1 (Ras related protein Rap1) and the cell adhesion molecule HEG1 (Heart of Glass 1) (Gingras et al, 2012; Gingras et al, 2013; Li et al, 2012). These structural studies have therefore provided insights into the molecular basis for the CCM complex proteins and their interactions (Fisher and Boggon, 2014), however gaps still remain in our structural understanding of KRIT1.…”