Related Experiment Video

Updated: Aug 11, 2026

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)
10:05

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)

Published on: January 20, 2016

Structural constraints for DNA recognition by Myc and other b-HLH-ZIP proteins: design of oncoprotein analogues

C Takemoto1, D E Fisher

  • 1Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

Gene Expression
|January 1, 1995
PubMed

Insights

Researchers engineered Myc oncoprotein analogues with enhanced DNA binding affinity. These modified proteins offer insights into transcription factor DNA recognition and potential therapeutic strategies.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • Transcription factors regulate gene expression and are crucial in human diseases.
  • The Myc oncoprotein, a key factor, recognizes specific DNA sequences like CACGTG.
  • Disrupting DNA recognition can significantly alter protein function.

Purpose of the Study:

  • To investigate the structural basis of DNA recognition by the Myc oncoprotein.
  • To engineer Myc analogues with improved DNA binding affinity.
  • To explore potential therapeutic applications based on understanding DNA recognition mechanisms.

Main Methods:

  • Structural analysis of the Myc basic region alpha helix involved in DNA binding.
  • Design and synthesis of Myc analogues with increased alanine content.
  • Assessment of spontaneous alpha helicity and DNA binding affinity of engineered analogues.

Main Results:

  • The Myc basic region alpha helix requires DNA binding for stabilization.
  • Engineered analogues with increased alanine content exhibited enhanced spontaneous alpha helicity.
  • These modifications led to significantly increased DNA binding affinity.

Conclusions:

  • The study elucidates structural constraints for DNA recognition by Myc and related proteins.
  • Enhanced DNA affinity can be achieved by increasing the intrinsic alpha helicity of the DNA-binding domain.
  • These findings provide a foundation for designing small molecule therapeutics targeting transcription factors.

More Related Videos

Tools to Study the Role of Architectural Protein HMGB1 in the Processing of Helix Distorting, Site-specific DNA Interstrand Crosslinks12:19

Tools to Study the Role of Architectural Protein HMGB1 in the Processing of Helix Distorting, Site-specific DNA Interstrand Crosslinks

Published on: November 10, 2016

CD Spectroscopy to Study DNA-Protein Interactions06:48

CD Spectroscopy to Study DNA-Protein Interactions

Published on: February 10, 2022

Related Concept Videos

Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
DNA Helicases00:55

DNA Helicases

DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...