Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

3.3K
3.3K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

9.5K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
9.5K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

2.8K
2.8K
Allosteric Regulation01:08

Allosteric Regulation

64.9K
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
64.9K
Allosteric Regulation01:08

Allosteric Regulation

16.5K
16.5K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

6.0K
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...
6.0K

You might also read

Related Articles

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

Sort by
Same author

AIntibody: an experimentally validated in silico antibody discovery design challenge.

Nature biotechnology·2024
Same author

The structure of NAD<sup>+</sup> consuming protein Acinetobacter baumannii TIR domain shows unique kinetics and conformations.

The Journal of biological chemistry·2023
Same author

Emergence of allostery through reorganization of protein residue network architecture.

The Journal of chemical physics·2023
Same author

Structure and dynamics of an α-fucosidase reveal a mechanism for highly efficient IgG transfucosylation.

Nature communications·2020
Same author

Structure of the cell-binding component of the <i>Clostridium difficile</i> binary toxin reveals a di-heptamer macromolecular assembly.

Proceedings of the National Academy of Sciences of the United States of America·2020
Same author

Tuning Allostery through Integration of Disorder to Order with a Residue Network.

Biochemistry·2020

Related Experiment Video

Updated: Apr 16, 2026

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
08:00

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

1.2K

Allosteric coupling via distant disorder-to-order transitions.

Christopher Eginton1, William J Cressman1, Sharrol Bachas2

  • 1Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.

Journal of Molecular Biology
|March 10, 2015
PubMed
Summary

Intrinsically disordered proteins utilize disorder-to-order transitions to achieve allosteric coupling. In the E. coli biotin repressor, this mechanism links ligand binding to dimerization via distant functional surfaces.

Keywords:
allosterycoupled equilibriadisorder-to-orderprotein:ligand interactionsprotein:protein interactions

More Related Videos

Excitonic Hamiltonians for Calculating Optical Absorption Spectra and Optoelectronic Properties of Molecular Aggregates and Solids
08:04

Excitonic Hamiltonians for Calculating Optical Absorption Spectra and Optoelectronic Properties of Molecular Aggregates and Solids

Published on: May 27, 2020

9.1K
Fabrication and Characterization of Disordered Polymer Optical Fibers for Transverse Anderson Localization of Light
09:19

Fabrication and Characterization of Disordered Polymer Optical Fibers for Transverse Anderson Localization of Light

Published on: July 29, 2013

12.0K

Related Experiment Videos

Last Updated: Apr 16, 2026

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
08:00

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

1.2K
Excitonic Hamiltonians for Calculating Optical Absorption Spectra and Optoelectronic Properties of Molecular Aggregates and Solids
08:04

Excitonic Hamiltonians for Calculating Optical Absorption Spectra and Optoelectronic Properties of Molecular Aggregates and Solids

Published on: May 27, 2020

9.1K
Fabrication and Characterization of Disordered Polymer Optical Fibers for Transverse Anderson Localization of Light
09:19

Fabrication and Characterization of Disordered Polymer Optical Fibers for Transverse Anderson Localization of Light

Published on: July 29, 2013

12.0K

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Background:

  • Allosteric coupling in proteins is crucial for biological regulation.
  • The precise mechanisms by which intrinsic disorder facilitates allostery are not fully understood.
  • The Escherichia coli biotin repressor (BirA) exhibits allosteric coupling between effector binding and dimerization.

Purpose of the Study:

  • To elucidate the role of intrinsic disorder in mediating allosteric coupling in BirA.
  • To investigate the structural and functional consequences of mutations affecting allosteric communication.
  • To understand how disorder-to-order transitions contribute to the protein's regulatory function.

Main Methods:

  • X-ray crystallography to determine protein structure.
  • Site-directed mutagenesis to create protein variants.
  • Functional assays to measure allosteric coupling and ligand binding.

Main Results:

  • Wild-type BirA exhibits significant allosteric coupling (-4.0 ± 0.3 kcal/mol) driven by loop folding upon effector binding.
  • A specific alanine substitution abolished this coupling, resulting in a monomeric, corepressor-bound state.
  • Structural analysis revealed that key loops involved in effector binding and dimerization become disordered in the mutant, contrasting with the folded state in the wild-type.

Conclusions:

  • Allosteric coupling in BirA is achieved through reciprocal communication of disorder-to-order transitions between distant functional surfaces.
  • Intrinsic disorder plays a critical role in transmitting allosteric signals.
  • The interplay between ordered and disordered states is essential for the integrated function of BirA.