3PT6

Crystal structure of mouse DNMT1(650-1602) in complex with DNA

Summary for 3PT6

• Entry DOI: 10.2210/pdb3pt6/pdb
• Related: 3PT9 3PTA
• Descriptor: DNA (cytosine-5)-methyltransferase 1, DNA (5'-D(*TP*CP*CP*CP*GP*TP*GP*AP*GP*CP*CP*TP*CP*CP*GP*CP*AP*GP*G)-3'), DNA (5'-D(*CP*CP*TP*GP*CP*GP*GP*AP*GP*GP*CP*TP*CP*AP*CP*GP*GP*GP*A)-3'), ... (6 entities in total)
• Functional Keywords: maintenance dna methylation, transferase-dna complex, transferase/dna
• Biological source: Mus musculus (mouse)
• Cellular location: Nucleus: P13864
• Total number of polymer chains: 6
• Total formula weight: 240681.47

Authors

Song, J.,Patel, D.J. (deposition date: 2010-12-02, release date: 2010-12-29, Last modification date: 2024-02-21)

Primary citation

Song, J.,Rechkoblit, O.,Bestor, T.H.,Patel, D.J.
Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation.
Science, 331:1036-1040, 2011

PubMed Abstract: Maintenance of genomic methylation patterns is mediated primarily by DNA methyltransferase-1 (DNMT1). We have solved structures of mouse and human DNMT1 composed of CXXC, tandem bromo-adjacent homology (BAH1/2), and methyltransferase domains bound to DNA-containing unmethylated CpG sites. The CXXC specifically binds to unmethylated CpG dinucleotide and positions the CXXC-BAH1 linker between the DNA and the active site of DNMT1, preventing de novo methylation. In addition, a loop projecting from BAH2 interacts with the target recognition domain (TRD) of the methyltransferase, stabilizing the TRD in a retracted position and preventing it from inserting into the DNA major groove. Our studies identify an autoinhibitory mechanism, in which unmethylated CpG dinucleotides are occluded from the active site to ensure that only hemimethylated CpG dinucleotides undergo methylation.

PubMed: 21163962
DOI: 10.1126/science.1195380

Experimental method

X-RAY DIFFRACTION (3 Å)