Structural studies of cerebral cavernous malformations 2 (CCM2) reveal a folded helical domain at its C-terminus

► Limited proteolysis reveals a C-terminal domain in CCM2. ► The 1.9 Å crystal structure of the CCM2 C-terminal domain is determined. ► CCM2 C-terminal domain is structurally homologous to harmonin. ► We term this domain the CCM2 harmonin-homology domain, HHD. ► This domain may represent a regulated site of protein-protein interaction for CCM2.