HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Douglas, A. E. Articles by Handel, T. M. Search for Related Content PubMed PubMed Citation Articles by Douglas, A. E. Articles by Handel, T. M. Social Bookmarking                   What's this?

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

¹ Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, California 94720, USA
² Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California–San Diego, La Jolla, California 92093, USA
³ College of Medicine, University of Florida, Gainesville, Florida 32610, USA

(RECEIVED December 11, 2006; FINAL REVISION January 15, 2007; ACCEPTED January 23, 2007)

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-x_L, 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.

Keywords: M11L; poxvirus; apoptosis inhibitor; X-ray crystallography; Bcl-2 homology; fluorescence polarization; immunomodulation

CiteULike

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				K. L. Norris and R. J. Youle Cytomegalovirus Proteins vMIA and m38.5 Link Mitochondrial Morphogenesis to Bcl-2 Family Proteins J. Virol., July 1, 2008; 82(13): 6232 - 6243. [Abstract] [Full Text] [PDF]

				L. Banadyga, J. Gerig, T. Stewart, and M. Barry Fowlpox Virus Encodes a Bcl-2 Homologue That Protects Cells from Apoptotic Death through Interaction with the Proapoptotic Protein Bak J. Virol., October 15, 2007; 81(20): 11032 - 11045. [Abstract] [Full Text] [PDF]