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

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

7.6K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
7.6K
Drug-Receptor Interactions01:29

Drug-Receptor Interactions

4.8K
Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. For instance, the binding of agonists activates the receptor to generate a cellular reaction, while antagonists bind to receptors without causing their activation.
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
4.8K
Pore Transport and Ion-Pair Transport01:17

Pore Transport and Ion-Pair Transport

324
Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited  but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
324
Protein-protein Interfaces02:04

Protein-protein Interfaces

12.4K
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...
12.4K
Drug-Receptor Bonds01:25

Drug-Receptor Bonds

2.7K
Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...
2.7K
The Two-State Receptor Model01:29

The Two-State Receptor Model

1.9K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
1.9K

You might also read

Related Articles

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

Sort by
Same author

PIP <sub>2</sub> stabilizes Na <sub>V</sub> 1.5 gating and links receptor signaling to cardiac late sodium current.

bioRxiv : the preprint server for biology·2026
Same author

PfApiAT2 is a proline transporter essential for the transmission of Plasmodium falciparum by the mosquito vector.

Nature communications·2026
Same author

Ion Channel Nano-Diagnostics for ER+ Breast Cancer.

bioRxiv : the preprint server for biology·2026
Same author

PfApiAT2 is a proline transporter essential for the transmission of <i>Plasmodium falciparum</i> by the mosquito vector.

Research square·2026
Same author

Allosteric coupling between PIP<sub>2</sub> and Ca<sup>2+</sup> binding sites gates TMEM16A channels.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

PfApiAT2 is a proline transporter essential for the transmission of <i>Plasmodium falciparum</i> by the mosquito vector.

bioRxiv : the preprint server for biology·2026

Related Experiment Video

Updated: May 23, 2025

PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions
10:58

PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions

Published on: July 27, 2017

9.4K

Orthosteric interactions with PIP 2 activate TMEM16A channels.

J Xu, A Santa-Cruz, Aishwarya Chandrashekar

    Biorxiv : the Preprint Server for Biology
    |March 10, 2025
    PubMed
    Summary

    Researchers identified how phosphatidylinositol 4,5-bisphosphate (PIP2) interacts with TMEM16A channels. This interaction is crucial for channel gating and ion permeation, offering new avenues for drug development targeting TMEM16A-related diseases.

    More Related Videos

    Capturing the Interaction Kinetics of an Ion Channel Protein with Small Molecules by the Bio-layer Interferometry Assay
    10:41

    Capturing the Interaction Kinetics of an Ion Channel Protein with Small Molecules by the Bio-layer Interferometry Assay

    Published on: March 7, 2018

    8.2K
    Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
    08:07

    Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

    Published on: July 26, 2019

    8.5K

    Related Experiment Videos

    Last Updated: May 23, 2025

    PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions
    10:58

    PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions

    Published on: July 27, 2017

    9.4K
    Capturing the Interaction Kinetics of an Ion Channel Protein with Small Molecules by the Bio-layer Interferometry Assay
    10:41

    Capturing the Interaction Kinetics of an Ion Channel Protein with Small Molecules by the Bio-layer Interferometry Assay

    Published on: March 7, 2018

    8.2K
    Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
    08:07

    Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

    Published on: July 26, 2019

    8.5K

    Area of Science:

    • Membrane biophysics
    • Ion channel function
    • Molecular dynamics simulations

    Background:

    • TMEM16A channels conduct calcium-activated chloride currents vital for physiological processes.
    • Channel activation requires intracellular calcium and interaction with phosphatidylinositol 4,5-bisphosphate (PIP2).
    • The precise role and binding site of PIP2 in TMEM16A gating remain largely uncharacterized.

    Purpose of the Study:

    • To elucidate the specific PIP2 binding interactions governing TMEM16A channel gating and ion permeation.
    • To understand the molecular mechanisms underlying PIP2-mediated TMEM16A activation.

    Main Methods:

    • Gating molecular dynamics (GMD) simulations.
    • Electrophysiological assays.
    • Structural analysis of protein-lipid interactions.

    Main Results:

    • Identified specific interactions between the TMEM16A α4 helix and PIP2 headgroups and acyl chains.
    • Revealed that PIP2 binding opens an electrostatic ring and stabilizes the extracellular chloride permeation pathway.
    • Demonstrated the critical role of PIP2 in TMEM16A channel gating.

    Conclusions:

    • PIP2 plays a dynamic and essential role in TMEM16A channel function and activation.
    • The identified PIP2 binding site provides a framework for rational drug development targeting TMEM16A.
    • Findings offer insights into membrane protein-lipid interactions and ion channel gating mechanisms.