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QuickView for Zinc finger, SIAH-type (biogroup)
- Description:
- 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. SINA/Siah family proteins represent mammalian homologs of the Drosophila SINA (seven in absentia) protein. SINA is required for R7 photoreceptor cell differentiation within the sevenless pathway. Members of this family are E3 ubiquitin ligases that regulate ubiquitination and protein degradation. Siahs are known to recognise several target proteins including Deleted in Colorectal Cancer (DCC), synaptophysin and Numb and promote their degradation. SINA/Siah sequences are highly conserved from plants to mammals. Whereas the N terminus and RING domain of Siah bind E2 proteins, the C terminus can be considered as a substrate- and cofactor-interaction domain (substrate-binding domain, SBD) that interacts with a number of proteins, some of which are degraded. The SBD domain displays some sequence similarities with the C-terminal region of TRAF proteins. It contains a cysteine-rich region, the SIAH-type zinc finger, with eight totally conserved Cys and His residues that coordinate two zinc atoms. The crystal structure of SIAH-type zinc finger has been solved. It folds in two subdomains, each one binding one zinc atom and consisting of two beta-strands and an alpha helice.
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