2mb7 | pdb_00002mb7

Solution structure of MBD3 methylcytosine binding domain

spinqualitylabelsall models 2mb7, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2mb7 is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: MBD3 (HUMAN) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Although highly homologous to other methylcytosine binding domain (MBD) proteins, MBD3 does not selectively bind methylated DNA and thus the functional role of MBD3 remains in question. To explore the structural basis of its binding properties and potential function, we characterized the solution structure and binding distribution of the MBD3 MBD on hydroxymethylated, methylated and unmethylated DNA. The overall fold of this domain is very similar to other MBDs, yet a key loop involved in DNA binding is more disordered than previously observed. Specific recognition of methylated DNA constrains the structure of this loop and results in large chemical shift changes in NMR spectra. Based on these spectral changes, we show that MBD3 preferentially localizes to methylated and, to a lesser degree, unmethylated cytosine-guanosine dinucleotides (CpGs), yet does not distinguish between hydroxymethylated and unmethylated sites. Measuring residual dipolar couplings (RDCs) for the different bound states clearly shows that the MBD3 structure does not change between methylation specific and non-specific binding modes. Furthermore, RDCs measured for MBD3 bound to methylated DNA can be described by a linear combination of those for the methylation and non-specific binding modes, confirming the preferential localization to methylated sites. The highly homologous MBD2 protein shows similar but much stronger localization to methylated as well as unmethylated CpGs. Together, these data establish the structural basis for the relative distribution of MBD2 and MBD3 on genomic DNA and their observed occupancy at active and inactive CpG-rich promoters. Probing the Dynamic Distribution of Bound States for Methyl-cytosine Binding Domains on DNA.,Cramer JM, Scarsdale JN, Walavalkar NM, Buchwald WA, Ginder GD, Williams DC Jr J Biol Chem. 2013 Dec 4. PMID:24307175 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Methyl CpG binding protein

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