A truncated two-alpha-helix F-box present in poxvirus ankyrin-repeat proteins is sufficient for binding the SCF1 ubiquitin ligase complex.

Poxviruses encode a large family of ankyrin-repeat (ANK) proteins, most of which contain an F-box-like motif necessary for the interaction of the ANK proteins with SCF1 (Skp1-Cullin1-F-box) complexes. The viral motif is generally truncated compared with the three-alpha-helix cellular F-box. Cellular F-box alpha-helices 1-3 and regions C-terminal to them have been shown to contribute to Skp1 binding. We report that the poxvirus F-boxes generally contain only two alpha-helices, corresponding to cellular F-box alpha-helices 1 and 2. A third alpha-helix was detected in some poxvirus F-boxes, but was not predicted to interact with Skp1. All but one of the poxvirus ANK/F-box proteins examined terminated directly after the F-box, excluding any contribution by C-terminal regions to the binding of Skp1. Here we show that, despite this truncation, the F-box of a prototypical poxvirus ANK protein, containing two alpha-helices, is not only necessary but also sufficient for interaction with SCF1.