Poxvirus ankyrin repeat proteins are a unique class of F-box proteins that associate with cellular SCF1 ubiquitin ligase complexes

F-box proteins direct the degradation of an extensive range of proteins via the ubiquitin-proteasome system. Members of this large family of proteins are typically bipartite. They recruit specific substrates through a substrate-binding domain and, via the F-box, link these to core components of a ma...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-08, Vol.105 (31), p.10955-10960
Main Authors: Sonnberg, Stephanie, Seet, Bruce T, Pawson, Tony, Fleming, Stephen B, Mercer, Andrew A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino acids
Ankyrin Repeat - genetics
Ankyrins
Base Sequence
Binding sites
Biological Sciences
Cell Line
Cell lines
Cells
Chromatography, Liquid
F box proteins
F-Box Proteins - genetics
F-Box Proteins - metabolism
Humans
Immunoblotting
Immunoprecipitation
Molecular Sequence Data
Orf virus
Orf virus - genetics
Poxviridae
Poxvirus
Protein Structure, Tertiary - genetics
Proteins
Sequence Analysis, DNA
SKP Cullin F-Box Protein Ligases - genetics
SKP Cullin F-Box Protein Ligases - metabolism
Tandem Mass Spectrometry
Ubiquitination
Ubiquitins
Viruses
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Summary:F-box proteins direct the degradation of an extensive range of proteins via the ubiquitin-proteasome system. Members of this large family of proteins are typically bipartite. They recruit specific substrates through a substrate-binding domain and, via the F-box, link these to core components of a major class of ubiquitin ligases (SCF1). F-box proteins thus determine the specificity of SCF1-mediated ubiquitination. F-box-like motifs were recently detected in poxvirus ankyrin repeat (ANK) proteins but clear compositional differences to typical F-box proteins raise questions regarding the classification and function of the motif. Here we show that all five ANK proteins of a representative poxvirus, Orf virus, interact in vivo with core components of the SCF1 ubiquitin ligase complex. Interaction is dependent on the poxviral F-box-like motif and the adaptor subunit of the complex (SKP1). The viral protein does not block enzymatic activity of the complex. These observations identify the poxviral motif as a functional F-box. They also identify a new class of F-box that in contrast to cellular counterparts is truncated, has an extreme C-terminal location and is paired with an ANK protein-binding domain. ANK proteins constitute the largest family of poxviral proteins but their function and the significance of their abundance have remained an enigma. We propose that poxviruses use these unique ANK/F-box proteins to dictate target specificity to SCF1 ubiquitin ligases and thereby exploit the cell's ubiquitin-proteasome machinery.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0802042105