7Y3K

Structure of SALL4 ZFC4 bound with 16 bp AT-rich dsDNA

Summary for 7Y3K

• Entry DOI: 10.2210/pdb7y3k/pdb
• Descriptor: Sal-like protein 4, DNA (16-mer), ZINC ION, ... (5 entities in total)
• Functional Keywords: sall4, zinc finger, at-rich dna, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 27472.05

Authors

Ru, W.,Xu, C. (deposition date: 2022-06-11, release date: 2022-10-26, Last modification date: 2023-11-29)

Primary citation

Ru, W.,Koga, T.,Wang, X.,Guo, Q.,Gearhart, M.D.,Zhao, S.,Murphy, M.,Kawakami, H.,Corcoran, D.,Zhang, J.,Zhu, Z.,Yao, X.,Kawakami, Y.,Xu, C.
Structural studies of SALL family protein zinc finger cluster domains in complex with DNA reveal preferential binding to an AATA tetranucleotide motif.
J.Biol.Chem., 298:102607-102607, 2022

PubMed Abstract: The Spalt-like 4 transcription factor (SALL4) plays an essential role in controlling the pluripotent property of embryonic stem cells via binding to AT-rich regions of genomic DNA, but structural details on this binding interaction have not been fully characterized. Here, we present crystal structures of the zinc finger cluster 4 (ZFC4) domain of SALL4 (SALL4) bound with different dsDNAs containing a conserved AT-rich motif. In the structures, two zinc fingers of SALL4 recognize an AATA tetranucleotide. We also solved the DNA-bound structures of SALL3 and SALL4. These structures illuminate a common preference for the AATA tetranucleotide shared by ZFC4 of SALL1, SALL3, and SALL4. Furthermore, our cell biology experiments demonstrate that the DNA-binding activity is essential for SALL4 function as DNA-binding defective mutants of mouse Sall4 failed to repress aberrant gene expression in Sall4-/- mESCs. Thus, these analyses provide new insights into the mechanisms of action underlying SALL family proteins in controlling cell fate via preferential targeting to AT-rich sites within genomic DNA during cell differentiation.

PubMed: 36257403
DOI: 10.1016/j.jbc.2022.102607

Experimental method

X-RAY DIFFRACTION (2.501 Å)