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. Author manuscript; available in PMC: 2014 Feb 19.
Published in final edited form as: Nat Rev Microbiol. 2013 Mar 11;11(4):264–276. doi: 10.1038/nrmicro2992

Figure 3. The functional domains of polyomavirus large and small T antigens.

Figure 3

a | The amino-terminal DnaJ (J) domain is shared between small and large T antigens. Large T antigen also contains a retinoblastoma-associated protein (RB)-binding LXCXE motif, a threonine–proline–proline–lysine (TPPK) motif, a nuclear-localization sequence (NLS), a DNA-binding domain (DBD), a helicase domain and a host range and adenovirus helper function (HR–AH) domain. Small T antigen contains an amino-terminal J domain followed by a unique region that is not shared with large T antigen and contains two zinc-fingers. b | Large T antigen binds to many cellular proteins. The J domain recruits heat shock cognate 71 kDa protein (HSC70) homologues. The region between the J domain and LXCXE motif has been shown to bind independently to cullin 7 (CUL7), BUB1 and insulin receptor substrate 1 (IRS1). Merkel cell polyomavirus (MCPyV) large T antigen binds to the endosomal protein VPS39. The LXCXE domain binds to retinoblastoma-associated protein (RB) and related proteins (p107 and p130). Phosphorylation of the threonine residue in the TPPK motif is required for large T antigen-mediated viral DNA replication. The nuclear localization signal (NLS) binds specifically to KPNA family importin homologues. The DBD and helicase domains are required for viral replication and recruit cellular DNA replication factors (DNA polymerase-α catalytic subunit (POLA), the replication protein A complex (RPA) and the DNA primase complex (PRIM) for DBD; and EP300, CREBBP, p53 and DNA topoisomerase 1 (TOP1) for the helicase domain) to the replicating simian virus 40 (SV40) genome. The carboxyl termini of SV40, JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) large T antigens each contain a threonine residue (threonine 701 in SV40, threonine 691 in BKPyV and threonine 684 in JCPyV) that, when phosphorylated, competes with phosphorylated G1–S-specific cyclin E1 and MYC for binding to the cullin RING ligase substrate adaptor FBXW7. FAM111A has recently been implicated in the SV40 host range restriction and adenovirus helper function. c | Small T antigen binds specifically to the A and C subunits of protein phosphatase 2A (PP2A). d | Polyomavirus genome replication. Replication begins when the large T antigen DBD binds to the origin of replication. Two hexamers of large T antigen form in a head-to-head orientation at the origin. The helicase domains of the large T antigen hexamers initiate unwinding of viral DNA followed by bidirectional replication.