6z2a

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Structure of Clr4 mutant - F256A/F310A/F427A bound to SAH

Structural highlights

6z2a is a 2 chain structure with sequence from Schizosaccharomyces pombe 972h-. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.456Å
Ligands:MG, SAH, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CLR4_SCHPO Histone methyltransferase. Catalytic component of the rik1-associated E3 ubiquitin ligase complex that shows ubiquitin ligase activity and is required for histone H3K9 methylation. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting swi6/HP1 to methylated histones which leads to transcriptional silencing within centromeric heterochromatin, telomeric regions and at the silent mating-type loci.[1] [2]

Publication Abstract from PubMed

The SUV39 class of methyltransferase enzymes deposits histone H3 lysine 9 di- and trimethylation (H3K9me2/3), the hallmark of constitutive heterochromatin. How these enzymes are regulated to mark specific genomic regions as heterochromatic is poorly understood. Clr4 is the sole H3K9me2/3 methyltransferase in the fission yeast Schizosaccharomyces pombe, and recent evidence suggests that ubiquitination of lysine 14 on histone H3 (H3K14ub) plays a key role in H3K9 methylation. However, the molecular mechanism of this regulation and its role in heterochromatin formation remain to be determined. Our structure-function approach shows that the H3K14ub substrate binds specifically and tightly to the catalytic domain of Clr4, and thereby stimulates the enzyme by over 250-fold. Mutations that disrupt this mechanism lead to a loss of H3K9me2/3 and abolish heterochromatin silencing similar to clr4 deletion. Comparison with mammalian SET domain proteins suggests that the Clr4 SET domain harbors a conserved sensor for H3K14ub, which mediates licensing of heterochromatin formation.

SUV39 SET domains mediate crosstalk of heterochromatic histone marks.,Stirpe A, Guidotti N, Northall SJ, Kilic S, Hainard A, Vadas O, Fierz B, Schalch T Elife. 2021 Sep 15;10:e62682. doi: 10.7554/eLife.62682. PMID:34524082[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
8 reviews cite this structure
The molecular basis of heterochromatin assembly and epigenetic inheritance.
Grewal et al. (2023)
7 more
2 other articles
No citations found

See Also

References

  1. ↑ Horn PJ, Bastie JN, Peterson CL. A Rik1-associated, cullin-dependent E3 ubiquitin ligase is essential for heterochromatin formation. Genes Dev. 2005 Jul 15;19(14):1705-14. PMID:16024659 doi:http://dx.doi.org/10.1101/gad.1328005
  2. ↑ Ekwall K, Ruusala T. Mutations in rik1, clr2, clr3 and clr4 genes asymmetrically derepress the silent mating-type loci in fission yeast. Genetics. 1994 Jan;136(1):53-64. PMID:8138176
  3. ↑ Stirpe A, Guidotti N, Northall SJ, Kilic S, Hainard A, Vadas O, Fierz B, Schalch T. SUV39 SET domains mediate crosstalk of heterochromatic histone marks. Elife. 2021 Sep 15;10:e62682. PMID:34524082 doi:10.7554/eLife.62682

Contents


PDB ID 6z2a

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OCA

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