4NW3

Crystal structure of MLL CXXC domain in complex with a CpG DNA

Summary for 4NW3

• Entry DOI: 10.2210/pdb4nw3/pdb
• Descriptor: Histone-lysine N-methyltransferase 2A, 5'-D(*GP*CP*CP*AP*TP*CP*GP*AP*TP*GP*GP*C)-3', ZINC ION (3 entities in total)
• Functional Keywords: histone-lysine n-methyltransferase, cpg island, cg island, structural genomics consortium, sgc, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus . MLL cleavage product N320: Nucleus. MLL cleavage product C180: Nucleus: Q03164
• Total number of polymer chains: 3
• Total formula weight: 16262.92

Authors

Bian, C.,Tempel, W.,Chao, X.,Walker, J.R.,Bountra, C.,Weigelt, J.,Arrowsmith, C.H.,Edwards, A.M.,Min, J.,Structural Genomics Consortium (SGC) (deposition date: 2013-12-05, release date: 2014-04-23, Last modification date: 2023-09-20)

Primary citation

Xu, C.,Liu, K.,Lei, M.,Yang, A.,Li, Y.,Hughes, T.R.,Min, J.
DNA Sequence Recognition of Human CXXC Domains and Their Structural Determinants.
Structure, 26:85-95.e3, 2018

PubMed Abstract: The CXXC domain, first identified as the reader of unmodified CpG dinucleotide, plays important roles in epigenetic regulation by targeting various activities to CpG islands. Here we systematically measured and compared the DNA-binding selectivities of all known human CXXC domains by different binding assays, and complemented the existing function-based classification of human CXXC domains with a classification based on their DNA selectivities. Through a series of crystal structures of CXXC domains with DNA ligands, we unravel the molecular mechanisms of how these CXXC domains, including single CXXC domains and tandem CXXC-PHD domains, recognize distinct DNA ligands, which further supports our classification of human CXXC domains and also provides insights into selective recruitment of chromatin modifiers to their respective targets via CXXC domains recognizing different genomic DNA sequences. Our study facilitates the understanding of the relationship between the DNA-binding specificities of the CXXC proteins and their biological functions.

PubMed: 29276034
DOI: 10.1016/j.str.2017.11.022

Experimental method

X-RAY DIFFRACTION (2.82 Å)