9pec

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM structure of Arabidopsis thaliana Met1 (RFTS free)

Structural highlights

9pec is a 1 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:	Electron Microscopy, Resolution 3.29Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DNMT1_ARATH Maintains chromatin CpG methylation that plays a role in genomic imprinting, regulation of embryogenesis and seed viability. Required for proper patterns of CG DNA methylation in dividing cells. Required for MEA promoter methylation in seeds.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

Plant DNA METHYLTRANSFERASE 1 (MET1) is responsible for maintaining genome-wide CG methylation. Its dysregulation has been linked to profound biological disruptions, including genomic instability and developmental defects. However, the exact mechanism by which MET1 orchestrates these vital functions and coordinates its various domains to shape the plant-specific epigenome remains unknown. Here, we report the cryo-EM structure of Arabidopsis thaliana MET1 (AtMET1), revealing an autoinhibitory mechanism that governs its DNA methylation activity. Between the two replication-foci-target sequence (RFTS) domains in AtMET1, the second RFTS domain (RFTS2) directly associates with the methyltransferase (MTase) domain, thereby inhibiting substrate-binding activity. Compared to DNMT1, AtMET1 lacks the CXXC domain and its downstream autoinhibitory linker, featuring only limited RFTS2-MTase interactions, resulting in a much-reduced autoinhibitory contact. In line with this difference, the DNA methylation activity of AtMET1 displays less temperature dependence than that of DNMT1, potentially allowing MET1 to maintain its activity across diverse temperature conditions. We further report the structure of AtMET1 bound to hemimethylated CG (hmCG) DNA, unveiling the molecular basis for substrate binding and CG recognition by AtMET1, and an activation mechanism that involves a coordinated conformational shift between two structural elements of its active site. In addition, our combined structural and biochemical analysis highlights distinct functionalities between the two RFTS domains of AtMET1, unraveling their evolutionary divergence from the DNMT1 RFTS domain. Together, this study offers a framework for understanding the structure and mechanism of AtMET1, with profound implications for the maintenance of CG methylation in plants.

Structure and autoinhibitory regulation of MET1 in the maintenance of plant CG methylation.,Lu J, Chen X, Fang J, Li D, Le H, Zhong X, Song J Plant Cell. 2025 Oct 13:koaf246. doi: 10.1093/plcell/koaf246. PMID:41082549^[8]

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

References

↑ Soppe WJ, Jasencakova Z, Houben A, Kakutani T, Meister A, Huang MS, Jacobsen SE, Schubert I, Fransz PF. DNA methylation controls histone H3 lysine 9 methylation and heterochromatin assembly in Arabidopsis. EMBO J. 2002 Dec 2;21(23):6549-59. PMID:12456661 doi:10.1093/emboj/cdf657
↑ Kankel MW, Ramsey DE, Stokes TL, Flowers SK, Haag JR, Jeddeloh JA, Riddle NC, Verbsky ML, Richards EJ. Arabidopsis MET1 cytosine methyltransferase mutants. Genetics. 2003 Mar;163(3):1109-22. PMID:12663548 doi:10.1093/genetics/163.3.1109
↑ Saze H, Mittelsten Scheid O, Paszkowski J. Maintenance of CpG methylation is essential for epigenetic inheritance during plant gametogenesis. Nat Genet. 2003 May;34(1):65-9. PMID:12669067 doi:10.1038/ng1138
↑ Xiao W, Gehring M, Choi Y, Margossian L, Pu H, Harada JJ, Goldberg RB, Pennell RI, Fischer RL. Imprinting of the MEA Polycomb gene is controlled by antagonism between MET1 methyltransferase and DME glycosylase. Dev Cell. 2003 Dec;5(6):891-901. PMID:14667411 doi:10.1016/s1534-5807(03)00361-7
↑ Xiao W, Custard KD, Brown RC, Lemmon BE, Harada JJ, Goldberg RB, Fischer RL. DNA methylation is critical for Arabidopsis embryogenesis and seed viability. Plant Cell. 2006 Apr;18(4):805-14. PMID:16531498 doi:10.1105/tpc.105.038836
↑ Xiao W, Brown RC, Lemmon BE, Harada JJ, Goldberg RB, Fischer RL. Regulation of seed size by hypomethylation of maternal and paternal genomes. Plant Physiol. 2006 Nov;142(3):1160-8. PMID:17012404 doi:10.1104/pp.106.088849
↑ Kim M, Ohr H, Lee JW, Hyun Y, Fischer RL, Choi Y. Temporal and spatial downregulation of Arabidopsis MET1 activity results in global DNA hypomethylation and developmental defects. Mol Cells. 2008 Dec 31;26(6):611-5 PMID:18820427
↑ Lu J, Chen X, Fang J, Li D, Le H, Zhong X, Song J. Structure and autoinhibitory regulation of MET1 in the maintenance of plant CG methylation. Plant Cell. 2025 Oct 13:koaf246. PMID:41082549 doi:10.1093/plcell/koaf246

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9pec"

Categories: Arabidopsis thaliana | Large Structures | Chen X | Lu J | Song J

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9pec is ON HOLD  until Paper Publication
+==Cryo-EM structure of Arabidopsis thaliana Met1 (RFTS free)==
+<StructureSection load='9pec' size='340' side='right'caption='[[9pec]], [[Resolution|resolution]] 3.29&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9pec]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9PEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PEC FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.29&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9pec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9pec OCA], [https://pdbe.org/9pec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9pec RCSB], [https://www.ebi.ac.uk/pdbsum/9pec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9pec ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DNMT1_ARATH DNMT1_ARATH] Maintains chromatin CpG methylation that plays a role in genomic imprinting, regulation of embryogenesis and seed viability. Required for proper patterns of CG DNA methylation in dividing cells. Required for MEA promoter methylation in seeds.<ref>PMID:12456661</ref> <ref>PMID:12663548</ref> <ref>PMID:12669067</ref> <ref>PMID:14667411</ref> <ref>PMID:16531498</ref> <ref>PMID:17012404</ref> <ref>PMID:18820427</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Plant DNA METHYLTRANSFERASE 1 (MET1) is responsible for maintaining genome-wide CG methylation. Its dysregulation has been linked to profound biological disruptions, including genomic instability and developmental defects. However, the exact mechanism by which MET1 orchestrates these vital functions and coordinates its various domains to shape the plant-specific epigenome remains unknown. Here, we report the cryo-EM structure of Arabidopsis thaliana MET1 (AtMET1), revealing an autoinhibitory mechanism that governs its DNA methylation activity. Between the two replication-foci-target sequence (RFTS) domains in AtMET1, the second RFTS domain (RFTS2) directly associates with the methyltransferase (MTase) domain, thereby inhibiting substrate-binding activity. Compared to DNMT1, AtMET1 lacks the CXXC domain and its downstream autoinhibitory linker, featuring only limited RFTS2-MTase interactions, resulting in a much-reduced autoinhibitory contact. In line with this difference, the DNA methylation activity of AtMET1 displays less temperature dependence than that of DNMT1, potentially allowing MET1 to maintain its activity across diverse temperature conditions. We further report the structure of AtMET1 bound to hemimethylated CG (hmCG) DNA, unveiling the molecular basis for substrate binding and CG recognition by AtMET1, and an activation mechanism that involves a coordinated conformational shift between two structural elements of its active site. In addition, our combined structural and biochemical analysis highlights distinct functionalities between the two RFTS domains of AtMET1, unraveling their evolutionary divergence from the DNMT1 RFTS domain. Together, this study offers a framework for understanding the structure and mechanism of AtMET1, with profound implications for the maintenance of CG methylation in plants.
-Authors:
+Structure and autoinhibitory regulation of MET1 in the maintenance of plant CG methylation.,Lu J, Chen X, Fang J, Li D, Le H, Zhong X, Song J Plant Cell. 2025 Oct 13:koaf246. doi: 10.1093/plcell/koaf246. PMID:41082549<ref>PMID:41082549</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9pec" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Arabidopsis thaliana]]
+[[Category: Large Structures]]
+[[Category: Chen X]]
+[[Category: Lu J]]
+[[Category: Song J]]

9pec

From Proteopedia

Current revision

Cryo-EM structure of Arabidopsis thaliana Met1 (RFTS free)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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