4IRI

Auto-inhibited ERG Ets Domain-DNA Complex

Summary for 4IRI

• Entry DOI: 10.2210/pdb4iri/pdb
• Related: 4IRG 4IRH
• Descriptor: Transcriptional regulator ERG, DNA (5'-D(*GP*AP*CP*CP*GP*GP*AP*AP*GP*TP*GP*G)-3'), DNA (5'-D(*CP*CP*AP*CP*TP*TP*CP*CP*GP*GP*TP*C)-3'), ... (4 entities in total)
• Functional Keywords: winged helix-turn-helix, ets domain, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P11308
• Total number of polymer chains: 3
• Total formula weight: 22198.50

Authors

Regan, M.C.,Horanyi, P.S.,Pryor, E.E.,Sarver, J.L.,Cafiso, D.S.,Bushweller, J.H. (deposition date: 2013-01-14, release date: 2013-07-31, Last modification date: 2024-02-28)

Primary citation

Regan, M.C.,Horanyi, P.S.,Pryor, E.E.,Sarver, J.L.,Cafiso, D.S.,Bushweller, J.H.
Structural and dynamic studies of the transcription factor ERG reveal DNA binding is allosterically autoinhibited.
Proc.Natl.Acad.Sci.USA, 110:13374-13379, 2013

PubMed Abstract: The Ets-Related Gene (ERG) belongs to the Ets family of transcription factors and is critically important for maintenance of the hematopoietic stem cell population. A chromosomal translocation observed in the majority of human prostate cancers leads to the aberrant overexpression of ERG. We have identified regions flanking the ERG Ets domain responsible for autoinhibition of DNA binding and solved crystal structures of uninhibited, autoinhibited, and DNA-bound ERG. NMR-based measurements of backbone dynamics show that uninhibited ERG undergoes substantial dynamics on the millisecond-to-microsecond timescale but autoinhibited and DNA-bound ERG do not. We propose a mechanism whereby the allosteric basis of ERG autoinhibition is mediated predominantly by the regulation of Ets-domain dynamics with only modest structural changes.

PubMed: 23898196
DOI: 10.1073/pnas.1301726110

Experimental method

X-RAY DIFFRACTION (2.77 Å)