1MDM

INHIBITED FRAGMENT OF ETS-1 AND PAIRED DOMAIN OF PAX5 BOUND TO DNA

Summary for 1MDM

• Entry DOI: 10.2210/pdb1mdm/pdb
• Related: 1MD0
• Descriptor: PAX5/ETS BINDING SITE ON THE MB-1 PROMOTER, PAIRED BOX PROTEIN PAX-5, C-ETS-1 PROTEIN, ... (4 entities in total)
• Functional Keywords: transcription factor, ternary complex, autoinhibition, ets domain, paired domain, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q02548 P27577
• Total number of polymer chains: 4
• Total formula weight: 51310.60

Authors

Garvie, C.W.,Pufall, M.A.,Graves, B.J.,Wolberger, C. (deposition date: 2002-08-07, release date: 2002-12-11, Last modification date: 2024-02-14)

Primary citation

Garvie, C.W.,Pufall, M.A.,Graves, B.J.,Wolberger, C.
STRUCTURAL ANALYSIS OF THE AUTOINHIBITION OF ETS-1 AND ITS ROLE IN PROTEIN PARTNERSHIPS
J.Biol.Chem., 277:45529-45536, 2002

PubMed Abstract: The DNA-binding activity of the eukaryotic transcription factor Ets-1 (E26 avian erythroblastosis virus oncogene-E twenty-six) is negatively regulated by inhibitory regions that flank the ETS domain. Based on the results of solution studies, these N- and C-terminal inhibitory regions have been proposed to pack against the ETS domain and form an autoinhibitory module whose N terminus partially unfolds upon binding of Ets-1 to DNA. Mutations that disrupt autoinhibition of DNA binding also cause a structural change in the inhibitory region. We report here a crystallographic study of fragments of Ets-1 that provide structural details of the inhibitory module and the structural transition that accompanies DNA binding. The structures of free and DNA-bound Ets-1 fragments containing the ETS domain and the inhibitory regions confirm that the N-terminal inhibitory region contains two alpha-helices one of which unfolds upon Ets-1 binding to DNA. The observations from the crystal structure, coupled with mutagenesis experiments, allow us to propose a model for the inhibited form of Ets-1 and lend insight into the flexible interaction between Ets-1 and the acute myeloid leukemia 1 protein, AML1 (RUNX1).

PubMed: 12221090
DOI: 10.1074/jbc.M206327200

Experimental method

X-RAY DIFFRACTION (2.8 Å)