8SSU

ZnFs 3-11 of CCCTC-binding factor (CTCF) Complexed with 19mer DNA

Summary for 8SSU

• Entry DOI: 10.2210/pdb8ssu/pdb
• Descriptor: Transcriptional repressor CTCF,LIM domain-binding protein 1, DNA (19-MER) Strand I, DNA (19-MER) Strand II, ... (6 entities in total)
• Functional Keywords: protein-dna complex, dna binding protein, transcription factor, zinc fingers, insulator/chromatin architecture, transcription-dna complex, transcription, transcription/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 52444.35

Authors

Horton, J.R.,Yang, J.,Cheng, X. (deposition date: 2023-05-08, release date: 2023-08-02, Last modification date: 2023-09-20)

Primary citation

Yang, J.,Horton, J.R.,Liu, B.,Corces, V.G.,Blumenthal, R.M.,Zhang, X.,Cheng, X.
Structures of CTCF-DNA complexes including all 11 zinc fingers.
Nucleic Acids Res., 51:8447-8462, 2023

PubMed Abstract: The CCCTC-binding factor (CTCF) binds tens of thousands of enhancers and promoters on mammalian chromosomes by means of its 11 tandem zinc finger (ZF) DNA-binding domain. In addition to the 12-15-bp CORE sequence, some of the CTCF binding sites contain 5' upstream and/or 3' downstream motifs. Here, we describe two structures for overlapping portions of human CTCF, respectively, including ZF1-ZF7 and ZF3-ZF11 in complex with DNA that incorporates the CORE sequence together with either 3' downstream or 5' upstream motifs. Like conventional tandem ZF array proteins, ZF1-ZF7 follow the right-handed twist of the DNA, with each finger occupying and recognizing one triplet of three base pairs in the DNA major groove. ZF8 plays a unique role, acting as a spacer across the DNA minor groove and positioning ZF9-ZF11 to make cross-strand contacts with DNA. We ascribe the difference between the two subgroups of ZF1-ZF7 and ZF8-ZF11 to residues at the two positions -6 and -5 within each finger, with small residues for ZF1-ZF7 and bulkier and polar/charged residues for ZF8-ZF11. ZF8 is also uniquely rich in basic amino acids, which allows salt bridges to DNA phosphates in the minor groove. Highly specific arginine-guanine and glutamine-adenine interactions, used to recognize G:C or A:T base pairs at conventional base-interacting positions of ZFs, also apply to the cross-strand interactions adopted by ZF9-ZF11. The differences between ZF1-ZF7 and ZF8-ZF11 can be rationalized structurally and may contribute to recognition of high-affinity CTCF binding sites.

PubMed: 37439339
DOI: 10.1093/nar/gkad594

Experimental method

X-RAY DIFFRACTION (2.89 Å)