2lf8

Intramolecular regulation of the ETS Domain within ETV6 sequence R335 to R458

spinqualitylabelsall models 2lf8 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2lf8 is a 1 chain structure with sequence from Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ETV6_MOUSE Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'. Publication Abstract from PubMed ETV6 (or TEL), a transcriptional repressor belonging to the ETS family, is frequently involved in chromosomal translocations linked with human cancers. It displays a DNA-binding mode distinct from other ETS proteins due to the presence of a self-associating PNT domain. In this study, we used NMR spectroscopy to dissect the structural and dynamic bases for the autoinhibition of ETV6 DNA binding by sequences C-terminal to its ETS domain. The C-terminal inhibitory domain (CID) contains two helices, H4 and H5, which sterically block the DNA-binding interface of the ETS domain. Importantly, these appended helices are only marginally stable as revealed by amide hydrogen exchange and (15)N relaxation measurements. The CID is thus poised to undergo a facile conformational change as required for DNA binding. The CID also dampens millisecond timescale motions of the ETS domain hypothesized to be critical for the recognition of specific ETS target sequences. This work illustrates the use of appended sequences on conserved structural domains to generate biological diversity and complements previous studies of the allosteric mechanism of ETS1 autoinhibition to reveal both common and divergent features underlying the regulation of DNA binding by ETS transcription factors. Autoinhibition of ETV6 (TEL) DNA Binding: Appended Helices Sterically Block the ETS Domain.,Coyne HJ 3rd, De S, Okon M, Green SM, Bhachech N, Graves BJ, McIntosh LP J Mol Biol. 2012 Aug 3;421(1):67-84. Epub 2012 May 12. PMID:22584210 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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