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

Publication Type:

Journal Article

Authors:

Fisher, Oriana S; Zhang, Rong; Li, Xiaofeng; Murphy, James W; Demeler, Borries; Boggon, Titus J

Source:

FEBS Lett, Volume 587, Issue 3, p.272-7 (2013)

Keywords:

Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Binding Sites, Cadherins, Carrier Proteins, Crystallography, X-Ray, Humans, Models, Molecular, Molecular Sequence Data, Protein Folding, Protein Multimerization, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Homology, Amino Acid

Abstract:

<p>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.</p>

Detector: 
Q315
Beamline: 
24-ID-C