ZnF_C2C2

C2C2 Zinc finger
ZnF_C2C2
SMART accession number:SM00440
Description: Nucleic-acid-binding motif in transcriptional elongation factor TFIIS and RNA polymerases.
Interpro abstract (IPR001222):

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 [(PUBMED:10529348), (PUBMED:15963892), (PUBMED:15718139), (PUBMED:17210253), (PUBMED:12665246)]. 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 [(PUBMED:11179890)]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents a zinc finger motif found in transcription factor IIs (TFIIS). In eukaryotes the initiation of transcription of protein encoding genes by polymerase II (Pol II) is modulated by general and specific transcription factors. The general transcription factors operate through common promoters elements (such as the TATA box). At least eight different proteins associate to form the general transcription factors: TFIIA, -IIB, -IID, -IIE, -IIF, -IIG, -IIH and -IIS [(PUBMED:3346229)]. During mRNA elongation, Pol II can encounter DNA sequences that cause reverse movement of the enzyme. Such backtracking involves extrusion of the RNA 3'-end into the pore, and can lead to transcriptional arrest. Escape from arrest requires cleavage of the extruded RNA with the help of TFIIS, which induces mRNA cleavage by enhancing the intrinsic nuclease activity of RNA polymerase (Pol) II, past template-encoded pause sites [(PUBMED:10723030)]. TFIIS extends from the polymerase surface via a pore to the internal active site. Two essential and invariant acidic residues in a TFIIS loop complement the Pol II active site and could position a metal ion and a water molecule for hydrolytic RNA cleavage. TFIIS also induces extensive structural changes in Pol II that would realign nucleic acids in the active centre.

TFIIS is a protein of about 300 amino acids. It contains three regions: a variable N-terminal domain not required for TFIIS activity; a conserved central domain required for Pol II binding; and a conserved C-terminal C4-type zinc finger essential for RNA cleavage. The zinc finger folds in a conformation termed a zinc ribbon [(PUBMED:7626141)] characterised by a three-stranded antiparallel beta-sheet and two beta-hairpins. A backbone model for Pol II-TFIIS complex was obtained from X-ray analysis. It shows that a beta hairpin protrudes from the zinc finger and complements the pol II active site [(PUBMED:12914699)].

Some viral proteins also contain the TFIIS zinc ribbon C-terminal domain. The Vaccinia virus protein, unlike its eukaryotic homologue, is an integral RNA polymerase subunit rather than a readily separable transcription factor [(PUBMED:2398897)].

More information about these proteins can be found at Protein of the Month: Zinc Fingers [].

GO process:transcription, DNA-templated (GO:0006351)
GO function:zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676)
Family alignment:
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There are 3456 ZnF_C2C2 domains in 2494 proteins in SMART's nrdb database.

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