4qep

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crystal structure of KRYPTONITE in complex with mCHG DNA and SAH

Structural highlights

4qep is a 3 chain structure with sequence from Arabidopsis thaliana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.1Å
Ligands:5CM, SAH, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SUVH4_ARATH Histone methyltransferase. Methylates 'Lys-9' of histone H3. H3 'Lys-9' methylation represents a specific tag for epigenetic transcriptional repression. The silencing mechanism via DNA CpNpG methylation requires the targeting of chromomethylase CMT3 to methylated histones, probably through an interaction with an HP1-like adapter. By its function, KYP is directly required for the maintenance of the DNA CpNpG and asymmetric methylation. Involved in the silencing of transposable elements.[1] [2] [3] [4] [5]

Publication Abstract from PubMed

In Arabidopsis, CHG DNA methylation is controlled by the H3K9 methylation mark through a self-reinforcing loop between DNA methyltransferase CHROMOMETHYLASE3 (CMT3) and H3K9 histone methyltransferase KRYPTONITE/SUVH4 (KYP). We report on the structure of KYP in complex with methylated DNA, substrate H3 peptide, and cofactor SAH, thereby defining the spatial positioning of the SRA domain relative to the SET domain. The methylated DNA is bound by the SRA domain with the 5mC flipped out of the DNA, while the H3(1-15) peptide substrate binds between the SET and post-SET domains, with the epsilon-ammonium of K9 positioned adjacent to bound SAH. These structural insights, complemented by functional data on key mutants of residues lining the 5mC and H3K9-binding pockets within KYP, establish how methylated DNA recruits KYP to the histone substrate. Together, the structures of KYP and previously reported CMT3 complexes provide insights into molecular mechanisms linking DNA and histone methylation.

Mechanism of DNA Methylation-Directed Histone Methylation by KRYPTONITE.,Du J, Johnson LM, Groth M, Feng S, Hale CJ, Li S, Vashisht AA, Gallego-Bartolome J, Wohlschlegel JA, Patel DJ, Jacobsen SE Mol Cell. 2014 Jul 9. pii: S1097-2765(14)00491-2. doi:, 10.1016/j.molcel.2014.06.009. PMID:25018018[6]

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

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See Also

References

  1. ↑ Jackson JP, Lindroth AM, Cao X, Jacobsen SE. Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature. 2002 Apr 4;416(6880):556-60. Epub 2002 Mar 17. PMID:11898023 doi:http://dx.doi.org/10.1038/nature731
  2. ↑ Lindroth AM, Shultis D, Jasencakova Z, Fuchs J, Johnson L, Schubert D, Patnaik D, Pradhan S, Goodrich J, Schubert I, Jenuwein T, Khorasanizadeh S, Jacobsen SE. Dual histone H3 methylation marks at lysines 9 and 27 required for interaction with CHROMOMETHYLASE3. EMBO J. 2004 Oct 27;23(21):4286-96. Epub 2004 Sep 30. PMID:15457214 doi:http://dx.doi.org/10.1038/sj.emboj.7600430
  3. ↑ Johnson L, Mollah S, Garcia BA, Muratore TL, Shabanowitz J, Hunt DF, Jacobsen SE. Mass spectrometry analysis of Arabidopsis histone H3 reveals distinct combinations of post-translational modifications. Nucleic Acids Res. 2004 Dec 14;32(22):6511-8. Print 2004. PMID:15598823 doi:http://dx.doi.org/10.1093/nar/gkh992
  4. ↑ Tran RK, Zilberman D, de Bustos C, Ditt RF, Henikoff JG, Lindroth AM, Delrow J, Boyle T, Kwong S, Bryson TD, Jacobsen SE, Henikoff S. Chromatin and siRNA pathways cooperate to maintain DNA methylation of small transposable elements in Arabidopsis. Genome Biol. 2005;6(11):R90. Epub 2005 Oct 19. PMID:16277745 doi:http://dx.doi.org/10.1186/gb-2005-6-11-r90
  5. ↑ Ebbs ML, Bartee L, Bender J. H3 lysine 9 methylation is maintained on a transcribed inverted repeat by combined action of SUVH6 and SUVH4 methyltransferases. Mol Cell Biol. 2005 Dec;25(23):10507-15. PMID:16287862 doi:http://dx.doi.org/10.1128/MCB.25.23.10507-10515.2005
  6. ↑ Du J, Johnson LM, Groth M, Feng S, Hale CJ, Li S, Vashisht AA, Gallego-Bartolome J, Wohlschlegel JA, Patel DJ, Jacobsen SE. Mechanism of DNA Methylation-Directed Histone Methylation by KRYPTONITE. Mol Cell. 2014 Jul 9. pii: S1097-2765(14)00491-2. doi:, 10.1016/j.molcel.2014.06.009. PMID:25018018 doi:http://dx.doi.org/10.1016/j.molcel.2014.06.009

Contents


PDB ID 4qep

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