D
IPR001841

Zinc finger, RING-type

InterPro entry
Short nameZnf_RING
Overlapping
homologous
superfamilies
 
domain relationships

Description

This entry represents RING-type zinc finger domains. The RING-finger is a specialised type of Zn-finger of 40 to 60 residues that binds two atoms of zinc, and is probably involved in mediating protein-protein interactions
[6, 9, 5]
. There are two different variants, the C3HC4-type and a C3H2C3-type, which are clearly related despite the different cysteine/histidine pattern. The latter type is sometimes referred to as 'RING-H2 finger'. The RING domain is a protein interaction domain that has been implicated in a range of diverse biological processes. E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain. E3 ubiquitin-protein ligases determine the substrate specificity for ubiquitylation and have been classified into HECT and RING-finger families. More recently, however, U-box proteins, which contain a domain (the U box) of about 70 amino acids that is conserved from yeast to humans, have been identified as a new type of E3
[11]
. Various RING fingers also exhibit binding to E2 ubiquitin-conjugating enzymes (Ubc's)
[13, 12, 4]
.

Several 3D-structures for RING-fingers are known
[9, 5]
. The 3D structure of the zinc ligation system is unique to the RING domain and is referred to as the 'cross-brace' motif. The spacing of the cysteines in such a domain is C-x(2)-C-x(9 to 39)-C-x(1 to 3)-H-x(2 to 3)-C-x(2)-C-x(4 to 48)-C-x(2)-C. Metal ligand pairs one and three co-ordinate to bind one zinc ion, whilst pairs two and four bind the second.

Note that in the older literature, some RING-fingers are denoted as LIM-domains. The LIM-domain Zn-finger is a fundamentally different family, albeit with similar Cys-spacing (see
IPR001781
).

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
[1, 2, 3, 8, 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, to name but a few
[7]
. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

References

1.Zinc finger peptides for the regulation of gene expression. Klug A. J. Mol. Biol. 293, 215-8, (1999). View articlePMID: 10529348

2.Multiple modes of RNA recognition by zinc finger proteins. Hall TM. Curr. Opin. Struct. Biol. 15, 367-73, (2005). View articlePMID: 15963892

3.Zinc finger proteins: getting a grip on RNA. Brown RS. Curr. Opin. Struct. Biol. 15, 94-8, (2005). View articlePMID: 15718139

4.A new finger on the protein destruction button. Barinaga M. Science 286, 223, 225, (1999). View articlePMID: 10577187

5.Does this have a familiar RING? Saurin AJ, Borden KL, Boddy MN, Freemont PS. Trends Biochem. Sci. 21, 208-14, (1996). View articlePMID: 8744354

6.The RING finger. A novel protein sequence motif related to the zinc finger. Freemont PS. Ann. N. Y. Acad. Sci. 684, 174-92, (1993). View articlePMID: 8317827

7.Zinc finger proteins: new insights into structural and functional diversity. Laity JH, Lee BM, Wright PE. Curr. Opin. Struct. Biol. 11, 39-46, (2001). View articlePMID: 11179890

8.Sticky fingers: zinc-fingers as protein-recognition motifs. Gamsjaeger R, Liew CK, Loughlin FE, Crossley M, Mackay JP. Trends Biochem. Sci. 32, 63-70, (2007). View articlePMID: 17210253

9.The RING finger domain: a recent example of a sequence-structure family. Borden KL, Freemont PS. Curr. Opin. Struct. Biol. 6, 395-401, (1996). View articlePMID: 8804826

10.Zinc fingers--folds for many occasions. Matthews JM, Sunde M. IUBMB Life 54, 351-5, (2002). View articlePMID: 12665246

11.Ubiquitylation as a quality control system for intracellular proteins. Hatakeyama S, Nakayama KI. J. Biochem. 134, 1-8, (2003). View articlePMID: 12944364

12.The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase. Joazeiro CA, Wing SS, Huang H, Leverson JD, Hunter T, Liu YC. Science 286, 309-12, (1999). View articlePMID: 10514377

13.RING for destruction? Freemont PS. Curr. Biol. 10, R84-7, (2000). View articlePMID: 10662664

Cross References

Contributing Member Database Entries
This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.