6Z2A

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

Summary for 6Z2A

• Entry DOI: 10.2210/pdb6z2a/pdb
• Descriptor: Histone-lysine N-methyltransferase, H3 lysine-9 specific, ZINC ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (6 entities in total)
• Functional Keywords: h3k9 methyltransferase, heterochromatin, transferase
• Biological source: Schizosaccharomyces pombe (strain 972 / ATCC 24843); More
• Total number of polymer chains: 2
• Total formula weight: 67900.96

Authors

Stirpe, A.,Schalch, T. (deposition date: 2020-05-15, release date: 2021-05-26, Last modification date: 2024-01-24)

Primary citation

Stirpe, A.,Guidotti, N.,Northall, S.J.,Kilic, S.,Hainard, A.,Vadas, O.,Fierz, B.,Schalch, T.
SUV39 SET domains mediate crosstalk of heterochromatic histone marks.
Elife, 10:-, 2021

PubMed Abstract: 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 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 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.

PubMed: 34524082
DOI: 10.7554/eLife.62682

Experimental method

X-RAY DIFFRACTION (2.456 Å)