In molecular biology, a RING (short for Really Interesting New Gene) finger domain is a protein structural domain of zinc finger type which contains a C3HC4amino acid motif which binds two zinc cations (seven cysteines and one histidine arranged non-consecutively).[2][3][4][5] This protein domain contains 40 to 60 amino acids. Many proteins containing a RING finger play a key role in the ubiquitination pathway.
Zinc finger (Znf) domains are relatively small protein motifs that bind one or more zinc atoms, and which usually contain multiple finger-like protrusions that make tandem contacts with their target molecule. They bind DNA, RNA, protein and/or lipid substrates.[6][7][8][9][10] 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.[11] Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
Some Zn finger domains have diverged such that they still maintain their core structure, but have lost their ability to bind zinc, using other means such as salt bridges or binding to other metals to stabilise the finger-like folds.
Function
Many RING finger domains simultaneously bind ubiquitination enzymes and their substrates and hence function as ligases. Ubiquitination in turn targets the substrate protein for degradation.[12][13][14]
Structure
The RING finger domain has the consensus sequence C-X2-C-X[9-39]-C-X[1-3]-H-X[2-3]-C-X2-C-X[4-48]-C-X2-C.[2] where:
C is a conserved cysteine residue involved zinc coordination,
H is a conserved histidine involved in zinc coordination,
Zn is zinc atom, and
X is any amino acid residue.
The following is a schematic representation of the structure of the RING finger domain:[2]
x x x x x x x x x x x x x x x x x x C C C C x \ / x x \ / x x Zn x x Zn x C / \ H C / \ C x x x x x x x x x x x x x x x x x
Examples
Examples of human genes which encode proteins containing a RING finger domain include:
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In molecular biology the ZZ-type zinc finger domain is a type of protein domain that was named because of its ability to bind two zinc ions. These domains contain 4-6 Cys residues that participate in zinc binding, including a Cys-X2-Cys motif found in other zinc finger domains. These zinc fingers are thought to be involved in protein-protein interactions. The structure of the ZZ domain shows that it belongs to the family of cross-brace zinc finger motifs that include the PHD, RING, and FYVE domains. ZZ-type zinc finger domains are found in:
In molecular biology the B-box-type zinc finger domain is a short protein domain of around 40 amino acid residues in length. B-box zinc fingers can be divided into two groups, where types 1 and 2 B-box domains differ in their consensus sequence and in the spacing of the 7-8 zinc-binding residues. Several proteins contain both types 1 and 2 B-boxes, suggesting some level of cooperativity between these two domains.
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In molecular biology, GATA zinc fingers are zinc-containing domains found in a number of transcription factors. Some members of this class of zinc fingers specifically bind the DNA sequence (A/T)GATA(A/G) in the regulatory regions of genes., giving rise to the name of the domain. In these domains, a single zinc ion is coordinated by 4 cysteine residues. NMR studies have shown the core of the Znf to comprise 2 irregular anti-parallel beta-sheets and an alpha-helix, followed by a long loop to the C-terminal end of the finger. The N-terminal part, which includes the helix, is similar in structure, but not sequence, to the N-terminal zinc module of the glucocorticoid receptor DNA-binding domain. The helix and the loop connecting the 2 beta-sheets interact with the major groove of the DNA, while the C-terminal tail wraps around into the minor groove. Interactions between the Znf and DNA are mainly hydrophobic, explaining the preponderance of thymines in the binding site; a large number of interactions with the phosphate backbone have also been observed. Two GATA zinc fingers are found in GATA-family transcription factors. However, there are several proteins that only contain a single copy of the domain. It is also worth noting that many GATA-type Znfs have not been experimentally demonstrated to be DNA-binding domains. Furthermore, several GATA-type Znfs have been demonstrated to act as protein-recognition domains. For example, the N-terminal Znf of GATA1 binds specifically to a zinc finger from the transcriptional coregulator FOG1 (ZFPM1).
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Solenoid protein domains are a highly modular type of protein domain. They consist of a chain of nearly identical folds, often simply called tandem repeats. They are extremely common among all types of proteins, though exact figures are unknown.
Ubiquitin-binding domains (UBDs) are protein domains that recognise and bind non-covalently to ubiquitin through protein-protein interactions. As of 2019, a total of 29 types of UBDs had been identified in the human proteome. Most UBDs bind to ubiquitin only weakly, with binding affinities in the low to mid μM range. Proteins containing UBDs are known as ubiquitin-binding proteins or sometimes as "ubiquitin receptors".
Zinc Finger Protein 548 (ZNF548) is a human protein encoded by the ZNF548 gene which is located on chromosome 19. It is found in the nucleus and is hypothesized to play a role in the regulation of transcription by RNA Polymerase II. It belongs to the Krüppel C2H2-type zinc-finger protein family as it contains many zinc-finger repeats.
References
↑ Barlow PN, Luisi B, Milner A, Elliott M, Everett R (March 1994). "Structure of the C3HC4 domain by 1H-nuclear magnetic resonance spectroscopy. A new structural class of zinc-finger". J. Mol. Biol. 237 (2): 201–11. doi:10.1006/jmbi.1994.1222. PMID8126734.
1 2 3 Borden KL, Freemont PS (1996). "The RING finger domain: a recent example of a sequence-structure family". Curr. Opin. Struct. Biol. 6 (3): 395–401. doi:10.1016/S0959-440X(96)80060-1. PMID8804826.
↑ Hanson IM, Poustka A, Trowsdale J (1991). "New genes in the class II region of the human major histocompatibility complex". Genomics. 10 (2): 417–24. doi:10.1016/0888-7543(91)90327-B. PMID1906426.
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