Transcription factor interactions: basics on zippers: Current Opinion in Structural Biology 1991, 1:71–79

doi:10.1016/0959-440X(91)90014-K

Current Opinion in Structural Biology

Volume 1, Issue 1, February 1991, Pages 71-79

https://doi.org/10.1016/0959-440X(91)90014-K Get rights and content

Abstract

The bZIP protein family of transcription factors has expanded dramatically and now includes several subfamilies that collectively define a consensus sequence; this includes the seven-residue repeat of leucines and a small number of shared residues in the basic region. The structure of the leucine zipper, a parallel coiled-coil that is stabilized by hydrophobic interactions, has been well established. The basic region assumes an α-helical conformation on binding DNA; however, the detailed structure of this region, as well as the mechanism of sequence recognition, remains unresolved.

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This chapter discusses the recent development in designing novel sequence-specific DNA-binding peptides by using a combination of synthetic organic, biochemical, and molecular biological approaches to study the principles of molecular recognition associated with protein–DNA interactions. Understanding recognition from the chemical and physical standpoints requires a better understanding of the energetic differences between the specific and nonspecific protein–DNA interactions. The chapter describes model systems, which addresses the issues of protein–protein and protein–DNA recognition in far greater detail than is possible with the native protein systems. These peptide dimers apply a steric constraint on the two DNA contact regions of the dimeric peptides because the formation of well-ordered dimer determines the relative orientation of each monomer. Another role for the protein dimerization domain is to modulate the cooperativity of DNA binding by noncovalent protein–protein interactions. The protein–protein interaction plays an essential role in both enhancing the selectivity of specific DNA binding and increasing the sensitivity of equilibrium binding to changes in protein concentration. The chapter also presents the model systems with noncovalent dimerization domains.
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Citation Excerpt :
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Transcription factor interactions: basics on zippers: Current Opinion in Structural Biology 1991, 1:71–79

Abstract

Genes Dev

The Leucine Binding Zipper: a Hypothetical Structure Common to a New Class of DNA Binding Proteins

Science

Homology between the DNA-Binding Domain of the GCN4 Regulatory Protein of Yeast and the Carboxyl-Terminal Region of a Protein Coded for by the Oncogene jun

Design of DNA-Binding Peptides Based on the Leucine Zipper Motif

Science

The Role of the Leucine Zipper in the Fos-Jun Interaction

Nature

The Leucine Repeat Motif in Fos Protein Mediates Complex Formation with Jun/AP-1 and Is Required for Transformation

Cell

Parallel Association of Fos and Jun Leucine Zippers Juxtaposes DNA Binding Domains

Science

Leucine Repeats and an Adjacent DNA Binding Domain Mediate the Formation of Functional cFos-cJun Heterodimers

Science

Fos-Jun Interaction: Mutational Analysis of the Leucine Zipper Domain of Both Proteins

Genes Dev

Evidence that the Leucine Zipper is a Coiled Coil

Science

Secondary Structure of a Leucine-Zipper Determined by Nuclear Magnetic Resonance Spectroscopy

Biochemistry

Preferential Heterodimer Formation by Isolated Leucine Zippers from Fos and Jun

Science

Leucine Zippers of Fos, Jun and GCN4 Dictate Dimerization Specificity and Thereby Control DNA Binding

Nature

Changing Fos Oncoprotein to a Jun-Independent DNA-Binding Protein with GCN4 Dimerization Specificity by Swapping Leucine Zippers

Nature

The Basic Region of Fos Mediates Specific DNA Binding

EMBO J

Analysis of Dimerization and DNA Binding Functions in Fos and Jun by Domain-Swapping: Involvement of Residues Outside the Leucine Zipper/Basic Region

Oncogene

Domain Swapping Reveals the Modular Nature of Fos, Jun and CREB Proteins

Mol Cell Biol

Trans-Dominant Negative Mutants of Fos and Jun

Cognate DNA Binding Specificity Retained After Leucine Zipper Exchange Between GCN4 and C/EBP

Science