RING finger domain

Last updated
Zinc finger, C3HC4 type (RING finger)
1chc animated.gif
Structure of the C3HC4 domain. [1] Zinc ions are black spheres, coordinated by cysteines residues (blue).
Identifiers
Symbolzf-C3HC4
Pfam PF00097
Pfam clan CL0229
ECOD 376.1.1
InterPro IPR001841
SMART SM00184
PROSITE PDOC00449
SCOP2 1chc / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

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 C3HC4 amino 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. Conversely, proteins with RING finger domains are the largest type of ubiquitin ligases in the human genome. [6]

Contents

Zinc fingers

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. [7] [8] [9] [10] [11] 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. [12] 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. [13] [14] [15]

Meiotic recombination

During meiosis, crossing over between homologous chromosomes (homologs) promotes accurate chromosome segregation. [16] In mammals, the ring-domain proteins RNF212, HEI10 and RNF212B facilitate crossing over between each pair of homologs during meiosis. [16] Studies in the mouse showed that these pro-crossover ring-domain proteins have distinct, but interdependent functions, in facilitating the homologous recombination and DNA repair processes that produce crossovers. [16]

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:

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:

AMFR, BARD1, BBAP, BFAR, BIRC2, BIRC3, BIRC7, BIRC8, BMI1, BRAP, BRCA1, CBL, CBLB, CBLC, CBLL1, CHFR, CNOT4, COMMD3, DTX1, DTX2, DTX3, DTX3L, DTX4, DZIP3, HCGV, HLTF, HOIL-1, IRF2BP2, LNX1, LNX2, LONRF1, LONRF2, LONRF3, MARCH1, MARCH10, MARCH2, MARCH3, MARCH4, MARCH5, MARCH6, MARCH7, MARCH8, MARCH9, MDM2, MEX3A, MEX3B, MEX3C, MEX3D, MGRN1, MIB1, MID1, MID2, MKRN1, MKRN2, MKRN3, MKRN4, MNAT1, MYLIP, NFX1, NFX2, PCGF1, PCGF2, PCGF3, PCGF4, PCGF5, PCGF6, PDZRN3, PDZRN4, PEX10, PHRF1, PJA1, PJA2, PML, PML-RAR, PXMP3, RAD18, RAG1, RAPSN, RBCK1, RBX1, RC3H1, RC3H2, RCHY1, RFP2, RFPL1, RFPL2, RFPL3, RFPL4B, RFWD2, RFWD3, RING1, RNF2, RNF4, RNF5, RNF6, RNF7, RNF8, RNF10, RNF11, RNF12, RNF13, RNF14, RNF19A, RNF20, RNF24, RNF25, RNF26, RNF32, RNF38, RNF39, RNF40, RNF41, RNF43, RNF44, RNF55, RNF71, RNF103, RNF111, RNF113A, RNF113B, RNF121, RNF122, RNF123, RNF125, RNF126, RNF128, RNF130, RNF133, RNF135, RNF138, RNF139, RNF141, RNF144A, RNF145, RNF146, RNF148, RNF149, RNF150, RNF151, RNF152, RNF157, RNF165, RNF166, RNF167, RNF168, RNF169, RNF170, RNF175, RNF180, RNF181, RNF182, RNF185, RNF207, RNF213, RNF215, RNFT1, SH3MD4, SH3RF1, SH3RF2, SYVN1, TIF1, TMEM118, TOPORS, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7, TRAIP, TRIM2, TRIM3, TRIM4, TRIM5, TRIM6, TRIM7, TRIM8, TRIM9, TRIM10, TRIM11, TRIM13, TRIM15, TRIM17, TRIM21, TRIM22, TRIM23, TRIM24, TRIM25, TRIM26, TRIM27, TRIM28, TRIM31, TRIM32, TRIM33, TRIM34, TRIM35, TRIM36, TRIM38, TRIM39, TRIM40, TRIM41, TRIM42, TRIM43, TRIM45, TRIM46, TRIM47, TRIM48, TRIM49, TRIM50, TRIM52, TRIM54, TRIM55, TRIM56, TRIM58, TRIM59, TRIM60, TRIM61, TRIM62, TRIM63, TRIM65, TRIM67, TRIM68, TRIM69, TRIM71, TRIM72, TRIM73, TRIM74, TRIML1, TTC3, UHRF1, UHRF2, VPS11, VPS8, ZNF179, ZNF294, ZNF313, ZNF364, ZNF451, ZNF650, ZNFB7, ZNRF1, ZNRF2, ZNRF3, ZNRF4, and ZSWIM2.

References

  1. ↑ 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. PMID   8126734.
  2. 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. PMID   8804826.
  3. ↑ 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. PMID   1906426.
  4. ↑ Freemont PS, Hanson IM, Trowsdale J (1991). "A novel cysteine-rich sequence motif". Cell. 64 (3): 483–4. doi: 10.1016/0092-8674(91)90229-R . PMID   1991318.
  5. ↑ Lovering R, Hanson IM, Borden KL, Martin S, O'Reilly NJ, Evan GI, Rahman D, Pappin DJ, Trowsdale J, Freemont PS (1993). "Identification and preliminary characterization of a protein motif related to the zinc finger". Proc. Natl. Acad. Sci. U.S.A. 90 (6): 2112–6. Bibcode:1993PNAS...90.2112L. doi: 10.1073/pnas.90.6.2112 . PMC   46035 . PMID   7681583.
  6. ↑ Scalia, Pierluigi; Williams, Stephen J.; Suma, Antonio; Carnevale, Vincenzo (2023-06-21). "The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer". Cells. 12 (13): 1680. doi: 10.3390/cells12131680 . ISSN   2073-4409. PMC   10340142 . PMID   37443713.
  7. ↑ Klug A (1999). "Zinc finger peptides for the regulation of gene expression". J. Mol. Biol. 293 (2): 215–8. doi:10.1006/jmbi.1999.3007. PMID   10529348.
  8. ↑ Hall TM (2005). "Multiple modes of RNA recognition by zinc finger proteins". Curr. Opin. Struct. Biol. 15 (3): 367–73. doi:10.1016/j.sbi.2005.04.004. PMID   15963892.
  9. ↑ Brown RS (2005). "Zinc finger proteins: getting a grip on RNA". Curr. Opin. Struct. Biol. 15 (1): 94–8. doi:10.1016/j.sbi.2005.01.006. PMID   15718139.
  10. ↑ Gamsjaeger R, Liew CK, Loughlin FE, Crossley M, Mackay JP (2007). "Sticky fingers: zinc-fingers as protein-recognition motifs". Trends Biochem. Sci. 32 (2): 63–70. doi:10.1016/j.tibs.2006.12.007. PMID   17210253.
  11. ↑ Matthews JM, Sunde M (2002). "Zinc fingers--folds for many occasions". IUBMB Life. 54 (6): 351–5. doi: 10.1080/15216540216035 . PMID   12665246. S2CID   22109146.
  12. ↑ Laity JH, Lee BM, Wright PE (2001). "Zinc finger proteins: new insights into structural and functional diversity". Curr. Opin. Struct. Biol. 11 (1): 39–46. doi:10.1016/S0959-440X(00)00167-6. PMID   11179890.
  13. ↑ Lorick KL, Jensen JP, Fang S, Ong AM, Hatakeyama S, Weissman AM (1999). "RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination". Proc. Natl. Acad. Sci. U.S.A. 96 (20): 11364–9. Bibcode:1999PNAS...9611364L. doi: 10.1073/pnas.96.20.11364 . PMC   18039 . PMID   10500182.
  14. ↑ Joazeiro CA, Weissman AM (2000). "RING finger proteins: mediators of ubiquitin ligase activity". Cell. 102 (5): 549–52. doi: 10.1016/S0092-8674(00)00077-5 . PMID   11007473.
  15. ↑ Freemont PS (2000). "RING for destruction?". Curr. Biol. 10 (2): R84–7. doi: 10.1016/S0960-9822(00)00287-6 . PMID   10662664.
  16. 1 2 3 Ito M, Yun Y, Kulkarni DS, Lee S, Sandhu S, Nuñez B, Hu L, Lee K, Lim N, Hirota RM, Prendergast R, Huang C, Huang I, Hunter N (January 2025). "Distinct and interdependent functions of three RING proteins regulate recombination during mammalian meiosis". Proc Natl Acad Sci U S A. 122 (2): e2412961121. doi:10.1073/pnas.2412961121. PMC   11745341 . PMID   39761402.
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