PS51287

Large T-antigen (T-ag) origin-binding domain (OBD) profile

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Member databasePROSITE profiles
PROSITE profiles typedomain
Short nameT_AG_OBD

Description

The group of polyomaviruses is formed by the homonymous murine virus (Py) as well as other representative members such as the simian virus 40 (SV40) and the human BK and JC viruses
[2]
. Their large T antigen (T-ag) protein binds to and activates DNA replication from the origine of DNA replication (ori). Insofar as is known, the T-ag binds to the origin first as a monomer to its pentanucleotide recognition element. The monomers are then thought to assemble into hexamers and double hexamers, which constitute the form that is active in initiation of DNA replication. When bound to the ori, T-ag double hexamers encircle DNA
[3]
. T-ag is a multidomain protein that contains an N-terminal J domain, a central origin-binding domain (OBD), and a C- terminal superfamily 3 helicase domain
[4]
. The overall fold of the ~130-residue T-ag OBD can be described as a central five-stranded antiparallel beta-sheet flanked by two alpha-helices on one side and one alpha-helix and one 3(10)-helix on the other. Both faces of the central beta-sheet are largely hydrophobic and are protected from solvent by the helices, thus forming two hydrophobic cores
[1]
. The T-ag OBD molecules are arranged as a spiral with a left-handed twist having six T-ag OBD's per turn. The spiral surrounds a central channel, the inner wall of which consists of alpha helices
[1]
. The profile we developed covers the entire T-ag OBD domain.

References

1.Solution structure of the origin DNA-binding domain of SV40 T-antigen. Luo X, Sanford DG, Bullock PA, Bachovchin WW. Nat. Struct. Biol. 3, 1034-9, (1996). View articlePMID: 8946857

2.Role of mouse polyomavirus late region in the control of viral DNA replication: a review. Iacoangeli A, Melucci-Vigo G, Risuleo G, Santi E. Biochimie 77, 780-6, (1995). View articlePMID: 8824775

3.Structure of the origin-binding domain of simian virus 40 large T antigen bound to DNA. Bochkareva E, Martynowski D, Seitova A, Bochkarev A. EMBO J. 25, 5961-9, (2006). View articlePMID: 17139255

4.Crystal structure of the simian virus 40 large T-antigen origin-binding domain. Meinke G, Bullock PA, Bohm A. J. Virol. 80, 4304-12, (2006). View articlePMID: 16611889

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