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

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.