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7y3i

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Structure of DNA bound SALL4

Structural highlights

7y3i is a 8 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.45Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SALL4_HUMAN Acro-renal-ocular syndrome;IVIC syndrome;Okihiro syndrome due to 20q13 microdeletion;Okihiro syndrome due to a point mutation. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

SALL4_HUMAN Transcription factor with a key role in the maintenance and self-renewal of embryonic and hematopoietic stem cells.^[1]

Publication Abstract from PubMed

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(ZFC4)) bound with different dsDNAs containing a conserved AT-rich motif. In the structures, two zinc fingers of SALL4(ZFC4) recognize an AATA tetranucleotide. We also solved the DNA-bound structures of SALL3(ZFC4) and SALL4(ZFC1). 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.

Structural studies of SALL family protein zinc finger cluster domains in complex with DNA reveal preferential binding to an AATA tetranucleotide motif.,Ru W, Koga T, Wang X, Guo Q, Gearhart MD, Zhao S, Murphy M, Kawakami H, Corcoran D, Zhang J, Zhu Z, Yao X, Kawakami Y, Xu C J Biol Chem. 2022 Dec;298(12):102607. doi: 10.1016/j.jbc.2022.102607. Epub 2022 , Oct 17. PMID:36257403^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yang F, Yao Y, Jiang Y, Lu L, Ma Y, Dai W. Sumoylation is important for stability, subcellular localization, and transcriptional activity of SALL4, an essential stem cell transcription factor. J Biol Chem. 2012 Nov 9;287(46):38600-8. doi: 10.1074/jbc.M112.391441. Epub 2012 , Sep 25. PMID:23012367 doi:http://dx.doi.org/10.1074/jbc.M112.391441
↑ Ru W, Koga T, Wang X, Guo Q, Gearhart MD, 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. 2022 Dec;298(12):102607. PMID:36257403 doi:10.1016/j.jbc.2022.102607