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

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

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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 1.9 Å 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 310 helix. This study provides the first structural characterization of CCM2. Structured summary of protein interactions: CCM2 binds to CCM3 by pull down (View interaction) CCM2 and CCM2 bind by X-ray crystallography (View interaction) CCM2 and CCM2 bind by molecular sieving (View interaction)

Original languageEnglish (US)
Pages (from-to)272-277
Number of pages6
JournalFEBS Letters
Issue number3
StatePublished - Jan 31 2013


  • Cerebral cavernous malformation
  • Harmonin-homology domain
  • Protein-protein interaction
  • Signal transduction
  • X-ray crystallography

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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