Structure of M11L: A myxoma virus structural homolog of the apoptosis inhibitor, Bcl-2

Andrew E. Douglas, Kevin D. Corbett, James M. Berger, Grant Mcfadden, Tracy M. Handel

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Apoptosis of virally infected cells is an innate host mechanism used to prevent viral spread. However, viruses have evolved a number of proteins that function to modulate the apoptotic cascades and thereby favor productive viral replication. One such antiapoptotic protein, myxoma virus M11L, has been shown to inhibit mitochondrial-dependent apoptosis by binding to and blocking the two executioner proteins Bak and Bax. Since M11L has no obvious sequence homology with Bcl-2 or Bcl-xL, the normal cellular inhibitors for Bak and Bax, and the structure of M11L has not been solved, the mode of binding to Bak and Bax is not known. In order to understand how M11L functions, the crystal structure of M11L was solved to 2.91 Å. Despite the lack of sequence similarity, M11L is a structural homolog of Bcl-2. Studies using a peptide derived from Bak indicate that M11L binds to Bak with a similar affinity (4.9 ± 0.3 μM) to the published binding affinities of Bcl-2 and Bcl-x L to the same peptide (12.7 μM and 0.5 μM, respectively), indicating that M11L inhibits apoptosis by mimicking and competing with host proteins for the binding of Bak and Bax. The structure provides important insight into how myxoma virus and other poxviruses facilitate viral dissemination by inhibiting mitochondrial dependent apoptosis. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish (US)
Pages (from-to)695-703
Number of pages9
JournalProtein Science
Issue number4
StatePublished - Apr 2007
Externally publishedYes


  • Apoptosis inhibitor
  • Bcl-2 homology
  • Fluorescence polarization
  • Immunomodulation
  • M11L
  • Poxvirus
  • X-ray crystallography

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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