PROSITE documentation PDOC51287

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

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 [1]. 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 [2]. T-ag is a multidomain protein that contains an N-terminal J domain (see <PDOC00553>), a central origin-binding domain (OBD), and a C-terminal superfamily 3 helicase domain (see <PDOC51206>) [3].

The overall fold of the ~130-residue T-ag OBD can be described as a central five-stranded antiparallel β-sheet flanked by two α-helices on one side and one α-helix and one 3(10)-helix on the other (see <PDB:1TBD>). Both faces of the central β-sheet are largely hydrophobic and are protected from solvent by the helices, thus forming two hydrophobic cores [4]. 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 α helices [4].

The profile we developed covers the entire T-ag OBD domain.