1ci6

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1ci6, resolution 2.6Å

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TRANSCRIPTION FACTOR ATF4-C/EBP BETA BZIP HETERODIMER

Overview

The crystal structure of the heterodimer formed by the basic leucine, zipper (bZIP) domains of activating transcription factor-4 (ATF4) and, CCAAT box/enhancer-binding protein beta (C/EBP beta), from two different, bZIP transcription factor families, has been determined and refined to 2.6, A. The structure shows that the heterodimer forms an asymmetric, coiled-coil. Even in the absence of DNA, the basic region of ATF4 forms a, continuous alpha-helix, but the basic region of C/EBP beta is disordered., Proteolysis, electrophoretic mobility shift assay, circular dichroism, and, NMR analyses indicated that (i) the bZIP domain of ATF4 is a disordered, monomer and forms a homodimer upon binding to the DNA target; (ii) the, bZIP domain of ATF4 forms a heterodimer with the bZIP domain of C/EBP beta, that binds the cAMP response element, but not CCAAT box DNA, with high, affinity; and (iii) the basic region of ATF4 has a higher alpha-helical, propensity than that of C/EBP beta. These results suggest that the degree, of ordering of the basic region and the fork and the dimerization, properties of the leucine zipper combine to distinguish the structurally, similar bZIP domains of ATF4 and C/EBP beta with respect to DNA target, sequence. This study provides insight into the mechanism by which dimeric, bZIP transcription factors discriminate between closely related but, distinct DNA targets.

About this Structure

1CI6 is a Protein complex structure of sequences from Homo sapiens and Mus musculus with and as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA., Podust LM, Krezel AM, Kim Y, J Biol Chem. 2001 Jan 5;276(1):505-13. PMID:11018027

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