Zinc finger, large T-antigen D1-type (Znf_lg_T-Ag_D1-typ)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents the zinc finger domain found in the large T-antigen (T-Ag) as the D1 domain. The T-Ag is found in a group of polyomaviruses consisting of the homonymous murine virus (Py) as well as other representative members such as the Simian virus 40 (SV40) and the human BK polyomavirus (BKPyV) and JC polyomavirus (JCPyV) . Their large T antigen (T-Ag) protein binds to and activates DNA replication from the origin 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 . T-Ag is a multi-domain protein that contains an N-terminal J domain, a central origin-binding domain (OBD), and a C-terminal superfamily 3 helicase domain . The helicase domain actually contains three distinct structural domains: D1 (domain 1), D2 and D3. D1 is the Zn domain at the N terminus and contains five α-helices (α1-α5). The Zn atom coordinated by a Zn motif is important in holding α3 (α-helix 3) and α4 together, which in turn provide an anchor for α1 and α2. The beginning of α5 packs with α1 and α2 of D1, but its C terminus extends to α6 of D3. The D2 domain contains three conserved helicase motifs related to SF3 helicases, namely the modified version of Walker A and B motifs and motif C. D2 folds into a core β-sheet consisting of five parallel β-strands sandwiched by α-helices. The third domain, D3, is all α-helical. Its seven α-helices originate from both the N-terminal region (α6-α8) and the C terminus (α13-α16), with D2 inserted between .

The Zn motif of T-Ag was proposed to form a canonical zinc-finger structure for DNA binding. However, the Zn domain (D1) has a globular fold stabilised by the coordination of a Zn atom through the Zn motif, and no classical zinc-finger structure specialised for DNA binding is present. The Zn motif is not directly involved in binding DNA but is instead important for stabilising the Zn-domain structure .