The zinc finger-associated domain (Znf-AD domain, also known as ZAD), is found at the N terminus of the C2H2 proteins of many arthropods [ PUBMED:12446571 ]. In vertebrates, only one protein containing an N-terminal structure similar to the ZAD has been found, Zinc finger protein 276. This domain forms an atypical treble-cleft-like … expand

The zinc finger-associated domain (Znf-AD domain, also known as ZAD), is found at the N terminus of the C2H2 proteins of many arthropods [ PUBMED:12446571 ]. In vertebrates, only one protein containing an N-terminal structure similar to the ZAD has been found, Zinc finger protein 276. This domain forms an atypical treble-cleft-like zinc co-ordinating fold. The Znf-AD domain is a protein-protein interaction module with the capability to form homodimers, but does not bind to DNA [ PUBMED:14604529 PUBMED:7569752 PUBMED:28740726 ].

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.