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

Allosteric Regulation01:08

Allosteric Regulation

57.6K
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...
57.6K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

8.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.7K
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

5.7K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.7K
Cell Signaling Feedback Loops01:07

Cell Signaling Feedback Loops

6.2K
Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
6.2K
T Cell Types and Functions01:24

T Cell Types and Functions

951
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
951
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

3.1K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.1K

You might also read

Related Articles

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

Sort by
Same author

Electrochemical DNA Hairpin Sensors for Differentiating Small Molecule Intercalation from Minor Groove Binding.

ArXiv·2026
Same author

Ready-to-load MHC-I nanoparticles for high-throughput T cell screening studies.

Science advances·2026
Same author

AE-PocketMiner Uses Attention to Simultaneously Predict Cryptic Pockets and Their Allosteric Coupling.

bioRxiv : the preprint server for biology·2026
Same author

A generalizable system for antigenic peptide targeting across HLA-I allotypes.

bioRxiv : the preprint server for biology·2026
Same author

Corrigendum to "<sup>19</sup>F NMR Strategy for Probing Site-specific RNA Dynamics in Large RNA-protein Complexes: Application to the Hfq RNA Chaperone" [J. Mol. Biol. 438 (2026) 169797].

Journal of molecular biology·2026
Same author

CD11c+ CD8 T cells cause IFN-γ-dependent autoimmune neuroinflammation that is restrained by PD-1 signaling.

JCI insight·2026
Same journal

DynaPIN: A tool for characterizing dynamic protein interfaces.

Journal of molecular biology·2026
Same journal

BindRNAgen: Protein-binding RNA sequence generation using latent diffusion models.

Journal of molecular biology·2026
Same journal

Structural basis of HSP90C, a highly active chloroplastic HSP90 chaperone from Arabidopsis thaliana.

Journal of molecular biology·2026
Same journal

Clinical inflammasome biomarkers: Progress and prospects.

Journal of molecular biology·2026
Same journal

Biologically Relevant, Cationic Residues in Human Rhinovirus Stabilize Capsid-Bound RNA Duplexes, and Restrict Capsid Flexibility.

Journal of molecular biology·2026
Same journal

Cryo-EM structures of phage T4 infection intermediate.

Journal of molecular biology·2026
See all related articles

Related Experiment Video

Updated: Jun 5, 2025

Isolation of Group 2 Innate Lymphoid Cells from Mouse Nasal Mucosa to Detect the Expression of CD226
08:30

Isolation of Group 2 Innate Lymphoid Cells from Mouse Nasal Mucosa to Detect the Expression of CD226

Published on: May 10, 2022

1.9K

Regulating IL-2 Immune Signaling Function Via A Core Allosteric Structural Network.

Claire H Woodward1, Shahlo O Solieva2, Daniel Hwang1

  • 1Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA; Center for Computational and Genomic Medicine, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Journal of Molecular Biology
|December 11, 2024
PubMed
Summary
This summary is machine-generated.

Interleukin-2 (IL-2) dynamics influence its function in T cell regulation. Modulating these dynamics offers a new strategy for developing targeted immunotherapies with reduced toxicity.

Keywords:
T cellsconformational exchangeinterleukin-2molecular dynamics simulationsnuclear magnetic resonance spectroscopy

More Related Videos

Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
11:55

Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade

Published on: March 14, 2011

14.5K
Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

15.1K

Related Experiment Videos

Last Updated: Jun 5, 2025

Isolation of Group 2 Innate Lymphoid Cells from Mouse Nasal Mucosa to Detect the Expression of CD226
08:30

Isolation of Group 2 Innate Lymphoid Cells from Mouse Nasal Mucosa to Detect the Expression of CD226

Published on: May 10, 2022

1.9K
Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
11:55

Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade

Published on: March 14, 2011

14.5K
Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

15.1K

Area of Science:

  • Immunology
  • Biochemistry
  • Structural Biology

Background:

  • Interleukin-2 (IL-2) is vital for T cell regulation, showing promise for cancer and autoimmune disease treatments.
  • Current IL-2 therapies face challenges due to pleiotropic effects causing toxicity and limited efficacy.
  • Previous research focused on receptor binding site modifications, neglecting IL-2's internal dynamics.

Purpose of the Study:

  • To characterize the dynamics of wild-type IL-2 and compare them to engineered "superkine" mutants (S15, S1).
  • To explore the role of intramolecular networks and allosteric pathways in IL-2 receptor recognition and function.
  • To investigate if modulating IL-2 dynamics can improve therapeutic potential and immune cell selectivity.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy to analyze protein dynamics.
  • Molecular Dynamics (MD) simulations to model IL-2 conformational changes.
  • Rational design of a specific mutation (L56A) to test the role of core network dynamics.

Main Results:

  • Significant differences in core dynamic pathways and conformational exchange rates were observed between wild-type IL-2 and the superkines.
  • Distinct allosteric networks and minor state conformations were identified in the S15 and S1 superkines.
  • The L56A mutation in S1 partially reverted its dynamics and function towards wild-type IL-2.
  • IL-2 superkine core dynamics are critical for enhanced receptor binding and effector T cell signaling.

Conclusions:

  • IL-2's internal dynamics and allosteric networks are key determinants of its function and receptor interactions.
  • Targeting IL-2's core dynamics represents a novel approach for engineering improved immunotherapies.
  • Modulating IL-2 dynamics can enhance immune cell selectivity, potentially leading to safer and more effective treatments.