7r78
From Proteopedia
cryo-EM structure of DNMT5 quaternary complex with hemimethylated DNA, AMP-PNP and SAH
Structural highlights
FunctionDMT5_CRYNH ATP-dependent cytosine methylase that maintains DNA methylation by acting at hemimethylated palindromic 5'-CG-3' sites to produce symmetrically methylated DNA strands (PubMed:24630728, PubMed:31955845, PubMed:32437639). DNA methylation may play a role in transcriptional silencing, particularly at transposable elements (PubMed:24630728).[1] [2] [3] [4] Publication Abstract from PubMedEpigenetic evolution occurs over million-year timescales in Cryptococcus neoformans and is mediated by DNMT5, the first maintenance type cytosine methyltransferase identified in the fungal or protist kingdoms, the first dependent on adenosine triphosphate (ATP), and the most hemimethyl-DNA-specific enzyme known. To understand these novel properties, we solved cryo-EM structures of CnDNMT5 in three states. These studies reveal an elaborate allosteric cascade in which hemimethylated DNA binding first activates the SNF2 ATPase domain by a large rigid body rotation while the target cytosine partially flips out of the DNA duplex. ATP binding then triggers striking structural reconfigurations of the methyltransferase catalytic pocket to enable cofactor binding, completion of base flipping, and catalysis. Bound unmethylated DNA does not open the catalytic pocket and is instead ejected upon ATP binding, driving high fidelity. This unprecedented chaperone-like, enzyme-remodeling role of the SNF2 ATPase domain illuminates how energy is used to enable faithful epigenetic memory. Structural insights into DNMT5-mediated ATP-dependent high-fidelity epigenome maintenance.,Wang J, Catania S, Wang C, de la Cruz MJ, Rao B, Madhani HD, Patel DJ Mol Cell. 2022 Feb 16. pii: S1097-2765(22)00104-6. doi:, 10.1016/j.molcel.2022.01.028. PMID:35202575[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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