title: Structural studies of cerebral cavernous malformations 2 (CCM2) reveal a folded helical domain at its C-terminus.
abstract: Cerebral cavernous malformations (CCM) are neurovascular dysplasias affecting up to 0.5% of the population. Mutations in the CCM2 gene are associated with acquisition of CCM. We identify a previously uncharacterized domain at the C-terminus of CCM2 and determine its 1.9Å resolution crystal structure. Because this domain is structurally homologous to the N-terminal domain of harmonin, we name it the CCM2 harmonin-homology domain or HHD. CCM2 HHD is observed in two conformations, and we employ analytical ultracentrifugation to test its oligomerization. Additionally, CCM2 HHD contains an unusually long 13-residue 3(10) helix. This study provides the first structural characterization of CCM2.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Oriana S
authors.initials: OS
authors.lastname: Fisher
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Li
authors.forename: James W
authors.initials: JW
authors.lastname: Murphy
authors.forename: Borries
authors.initials: B
authors.lastname: Demeler
authors.forename: Titus J
authors.initials: TJ
authors.lastname: Boggon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C502544:CCM2 protein, human; D015820:Cadherins; D002352:Carrier Proteins