8EO4

Human PU.1 ETS-Domain (165-270) Bound to d(AATAAGCGGAAGTGGG) with Di-methylated CpG sites

Summary for 8EO4

• Entry DOI: 10.2210/pdb8eo4/pdb
• Related: 8E3K 8E3R 8E4H 8E5Y 8EBH 8EE9 8EJ6 8EJ8 8EK3 8EK8 8EKJ 8EKU 8EKV 8EKZ 8EM9 8EMD 8ENG 8EO1
• Descriptor: DNA (5'-D(*AP*AP*TP*AP*AP*GP*CP*GP*GP*AP*AP*GP*TP*GP*GP*G)-3'), DNA (5'-D(*TP*CP*CP*CP*AP*CP*TP*TP*CP*CP*GP*CP*TP*TP*AP*T)-3'), Transcription factor PU.1, ... (5 entities in total)
• Functional Keywords: transcription factor, protein-dna complex, ets family, ets, pu.1, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 22284.01

Authors

Terrell, J.R.,Poon, G.M.K. (deposition date: 2022-10-02, release date: 2023-07-05, Last modification date: 2023-10-25)

Primary citation

Terrell, J.R.,Taylor, S.J.,Schneider, A.L.,Lu, Y.,Vernon, T.N.,Xhani, S.,Gumpper, R.H.,Luo, M.,Wilson, W.D.,Steidl, U.,Poon, G.M.K.
DNA selection by the master transcription factor PU.1.
Cell Rep, 42:112671-112671, 2023

PubMed Abstract: The master transcriptional regulator PU.1/Spi-1 engages DNA sites with affinities spanning multiple orders of magnitude. To elucidate this remarkable plasticity, we have characterized 22 high-resolution co-crystallographic PU.1/DNA complexes across the addressable affinity range in myeloid gene transactivation. Over a purine-rich core (such as 5'-GGAA-3') flanked by variable sequences, affinity is negotiated by direct readout on the 5' flank via a critical glutamine (Q226) sidechain and by indirect readout on the 3' flank by sequence-dependent helical flexibility. Direct readout by Q226 dynamically specifies PU.1's characteristic preference for purines and explains the pathogenic mutation Q226E in Waldenström macroglobulinemia. The structures also reveal how disruption of Q226 mediates strand-specific inhibition by DNA methylation and the recognition of non-canonical sites, including the authentic binding sequence at the CD11b promoter. A re-synthesis of phylogenetic and structural data on the ETS family, considering the centrality of Q226 in PU.1, unifies the model of DNA selection by ETS proteins.

PubMed: 37352101
DOI: 10.1016/j.celrep.2023.112671

Experimental method

X-RAY DIFFRACTION (1.24 Å)