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SV40 Large T Antigen

Introduction

The SV40 large T antigen is a multifunctional regulatory protein encoded by Simian Virus 40. It belongs to the AAA+ family of helicases ^[1]. The protein is responsible for initiation of DNA replication, regulation of transcription and alteration of the host cell cycle to promote infectivity. Large T antigen is an early gene product of SV40 and is translated via differential mRNA splicing.

Structure

T-antigen consists of an N-terminal J domain, a central origin-binding domain, and a C-terminal helicase domain ^[1].

spinqualitylabelsall models The origin binding domain of SV40 T antigen (PDB entry 1tbd) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image The Origin Binding Domain The central obd monomer consists of a five-stranded anti-parallel beta sheet flanked by two pairs of alpha helices. These molecules arrange tightly into a hexameric left-handed spiral, with 6 obd's per turn. Side-side interaction is crucial in hexamerization, for which residues Phe 183 and Ser 185 are crucial. The conformation creates a central channel 60 Angstroms wide, large enough for double stranded DNA, and is positively charged. The pitch of the spiral complements that of the DNA, bringing the sequence-specific loops of the obd's near the GAGGC pentanucleotides of the origin. Along the inner surface of the channel, the residues implicated in DNA binding are Asn 153, Arg 154, Thr 155 from the A motif; His 203, Arg 204 from the B2 motif; as well as His 201 and Arg 202. [1].

spinqualitylabelsall models The helicase domain Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Helicase The monomer of the helicase contains a AAA+ domain. Each monomer binds to and hydrolyzes an ATP and drives an overall conformational change in the hexamer. Presence of magnesium ion is necessary for hydrolysis.