8smj

From Proteopedia

Chimeric ETS-domain of murine PU.1 harboring the corresponding beta-strand 3 (S3) residues from murine Ets-1 in complex with d(AATAAGCGGAATGGGG)

Structural highlights

8smj is a 3 chain structure with sequence from Mus musculus 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 1.39Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SPI1_MOUSE Note=Involved in murine acute Friend erythroleukemia. It is a target region for SFFV proviral insertion.

Function

SPI1_MOUSE Binds to the PU-box, a purine-rich DNA sequence (5'-GAGGAA-3') that can act as a lymphoid-specific enhancer. This protein is a transcriptional activator that may be specifically involved in the differentiation or activation of macrophages or B-cells. Also binds RNA and may modulate pre-mRNA splicing.^[1]

Publication Abstract from PubMed

Nucleobases such as inosine have been extensively utilized to map direct contacts by proteins in the DNA groove. Their deployment as targeted probes of dynamics and hydration, which are dominant thermodynamic drivers of affinity and specificity, has been limited by a paucity of suitable experimental models. We report a joint crystallographic, thermodynamic, and computational study of the bidentate complex of the arginine side chain with a Watson-Crick guanine (ArgxGC), a highly specific configuration adopted by major transcription factors throughout the eukaryotic branches in the Tree of Life. Using the ETS-family factor PU.1 as a high-resolution structural framework, inosine substitution for guanine resulted in a sharp dissection of conformational dynamics and hydration and elucidated their role in the DNA specificity of PU.1. Our work suggests an under-exploited utility of modified nucleobases in untangling the structural thermodynamics of interactions, such as the ArgxGC motif, where direct and indirect readout are tightly integrated.

Dissection of integrated readout reveals the structural thermodynamics of DNA selection by transcription factors.,Vernon TN, Terrell JR, Albrecht AV, Germann MW, Wilson WD, Poon GMK Structure. 2024 Jan 4;32(1):83-96.e4. doi: 10.1016/j.str.2023.11.003. Epub 2023 , Dec 1. PMID:38042148^[2]

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

References

↑ Hallier M, Tavitian A, Moreau-Gachelin F. The transcription factor Spi-1/PU.1 binds RNA and interferes with the RNA-binding protein p54nrb. J Biol Chem. 1996 May 10;271(19):11177-81. PMID:8626664
↑ Vernon TN, Terrell JR, Albrecht AV, Germann MW, Wilson WD, Poon GMK. Dissection of integrated readout reveals the structural thermodynamics of DNA selection by transcription factors. Structure. 2024 Jan 4;32(1):83-96.e4. PMID:38042148 doi:10.1016/j.str.2023.11.003