Characterization of an amino-terminal dimerization domain from retroviral restriction factor Fv1.
The Fv1 protein is an endogenous factor in mice that confers resistance to infection by certain classes of murine leukemia virus, a phenomenon referred to as restriction. The mechanism of restriction is not understood, and the low endogenous level of Fv1 in cells has prevented any biochemical or biophysical analysis of the protein. We have now purified recombinant Fv1(n) protein from a baculovirus system and demonstrate that Fv1 exists in a multimeric form. Furthermore, we have mapped the position of two domains within the protein using limited proteolysis. Biophysical characterization of the N-terminal domain reveals that it comprises a highly helical and extended dimeric structure. Based on these biochemical and biophysical data, we propose a model for the arrangement of domains in Fv1 and suggest that dimerization of the N-terminal domain is necessary for Fv1 function to allow the protein to interact with multiple capsid protomers in retroviral cores.
Bishop
Kate N
KN
Divisions of Virology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
Mortuza
Gulnahar B
GB
Howell
Steven
S
Yap
Melvyn W
MW
Stoye
Jonathan P
JP
Taylor
Ian A
IA
D000595:Amino Acid Sequence; D000818:Animals; D000090103:Antiviral Restriction Factors; D016367:Baculoviridae / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry; D002942:Circular Dichroism; D019281:Dimerization; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; C103189:Fv1 protein, mouse; D011506:Proteins; D011994:Recombinant Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases