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PROTEIN STRUCTURE REPORT

Vaccinia virus N1L protein resembles a B cell lymphoma-2 (Bcl-2) family protein

Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA

(RECEIVED July 20, 2006; FINAL REVISION August 21, 2006; ACCEPTED August 21, 2006)

Poxviruses encode immuno-modulatory proteins capable of subverting host defenses. The poxvirus vaccinia expresses a small 14-kDa protein, N1L, that is critical for virulence. We report the crystal structure of N1L, which reveals an unexpected but striking resemblance to host apoptotic regulators of the B cell lymphoma-2 (Bcl-2) family. Although N1L lacks detectable Bcl-2 homology (BH) motifs at the sequence level, we show that N1L binds with high affinity to the BH3 peptides of pro-apoptotic Bcl-2 family proteins in vitro, consistent with a role for N1L in modulating host antiviral defenses.

Keywords: poxvirus; vaccinia virus; virulence; crystal structure; Bcl-2; apoptosis

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