Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Conserved Binding Sites

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...

Conserved Binding Sites

Conserved Binding Sites

Covalently Linked Protein Regulators

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....

Ligand Binding and Linkage

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...

Protein-protein Interfaces

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...

Ligand Binding Sites

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Polysomal Profiling Coupled to Allele-Specific Proteomics Reveals an EIF4H TranSNP Allele Possessing Higher mRNA Translation Potential.

Molecular & cellular proteomics : MCP·2026

Same author

Author Correction: Cryo-EM structure of a natural RNA nanocage.

Nature·2025

Same author

Structural mechanism of mRNA decoding by mammalian GTPase GTPBP1.

Nature communications·2025

Same author

Structural mechanism of mRNA decoding by mammalian GTPase GTPBP1.

bioRxiv : the preprint server for biology·2025

Same author

Cryo-EM structure of a natural RNA nanocage.

Nature·2025

Same author

Characterization of small nucleolar RNA retaining transcripts in human normal and cancer cells.

Non-coding RNA research·2025

Search research articles

Related Experiment Video

Updated: Nov 21, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

The complex architecture of p53 binding sites.

Alon Senitzki¹, Jessy Safieh¹, Vasundhara Sharma²

¹Department of Biology, Technion - Israel Institute of Technology, Technion City, Haifa 3200003, Israel.

Nucleic Acids Research

|January 14, 2021

Summary

Tumor suppressor p53 binding to DNA is variable. Flanking DNA sequences and half-site arrangement fine-tune p53 interactions, optimizing its response to stress signals.

More Related Videos

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy

Published on: February 7, 2019

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

Related Experiment Videos

Last Updated: Nov 21, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy

Published on: February 7, 2019

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

Area of Science:

Molecular Biology
Genetics
Biochemistry

Background:

The tumor suppressor p53 protein regulates cellular responses to stress by binding to specific DNA sequences.
Variability in p53 binding and transactivation is linked to direct and indirect DNA recognition mechanisms.
Understanding how p53 optimizes its DNA interactions is crucial for comprehending cellular stress responses.

Purpose of the Study:

To investigate the mechanisms by which p53 optimizes its interaction with DNA response elements (REs).
To determine the role of flanking sequences and half-site arrangement in modulating p53 binding and activity.
To elucidate how selection pressure has fine-tuned p53 REs for regulated responses.

Main Methods:

Analysis of p53 response elements (REs) and their flanking sequences.
Investigation of hemi-specific p53 binding.
Assessment of the impact of flanking sequences on p53 binding and transactivation.
Examination of the arrangement and orientation of p53 half-sites within REs relative to transcription direction.

Main Results:

Hemi-specific p53 binding to REs is more common than previously thought.
Sequences flanking REs significantly modulate p53 binding and activity, with effects extending 4-5 base pairs.
The arrangement of p53 half-sites within REs, relative to transcription direction, is optimized by selection pressure.
The p21-5' RE exhibits a half-site orientation that minimizes the influence of flanking sequences.

Conclusions:

p53 DNA binding is a highly regulated process influenced by flanking DNA and RE structure.
The directionality and arrangement of p53 half-sites are critical for optimizing and controlling p53-mediated responses.
Specific RE designs, like the p21-5' RE, minimize external modulations for robust p53 activity.