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The leucine zipper domain of the Max gene product is not an autonomous dimerization site

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Summary

Transcriptional factors are proteins that bind to specific regulatory DNA sequences controlling the synthesis of RNA from DNA templates. Among such factors, increasing attention has been devoted to the Max gene product, the specific partner for the c-Myc oncoprotein. Productive DNA binding by Max requires dimerization, which is mediated by specific interactions of its helix-loop-helix leucine zipper binding domain. The Max-DNA complex crystallizes as a parallel, left-handed, four-helix bundle structure with the leucine zipper region forming a parallel coiled-coil. In this paper, it is shown by circular dichroism spectroscopy that the leucine zipper domain of the transcriptional factor described above (Max 75–103) is not an autonomous folding unit. The lack of dimerization function has been ascribed to the probably destabilizing effect of histidine and asparagine residues at the dimerization interface. The hydrophobic mutation of one of these amino acids (Asn92 → Val) results in the formation of a coiled-coil structure.

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Abbreviations

bHLH:

basic helix-loop-helix

bLZip:

basic leucine zipper

CD:

circular dichroism

DNA:

deoxyribonucleic acid

EDT:

ethanedithiol

Fmoc:

fluorenylmethoxycarbonyl

GCN4:

general control protein 4

HLH:

helix-loop-helix

LZip:

leucine zipper

HPLC:

high-performance liquid chromatography

MALDI-TOF:

matrix-assisted laser-desorption ionization time-of-flight mass spectrometry

MBHA:

4-methylbenzhydrylamine (resin)

PAL:

tris(alkoxy)benzylamide linker

PEG:

polyethylene glycol

TFA:

trifluoroacetic acid

TFE:

2,2,2,-trifluoroethanol

Tm :

melting temperature at which 50% of the helicity is lost

tR :

retention time

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Authors and Affiliations

  1. Pharmaceuticals Division, Ciba-Geigy Ltd., CH-4002, Basel, Switzerland

    Carlos García-Echeverría

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  1. Carlos García-Echeverría
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Additional information

Amino acid symbols denote the l-configuration. Abbreviations used for amino acids follow the recommendations of the IUPAC-IUB Commission of Biochemical Nomenclature [Eur. J. Biochem., 138 (1984) 9].

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García-Echeverría, C. The leucine zipper domain of the Max gene product is not an autonomous dimerization site. Lett Pept Sci 1, 255–262 (1995). https://doi.org/10.1007/BF00127272

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  • DOI: https://doi.org/10.1007/BF00127272

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