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Related Concept Videos

Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

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Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
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Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

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Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
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The Role of Ion Channels in Neuronal Computation01:19

The Role of Ion Channels in Neuronal Computation

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A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
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Ion Channels01:19

Ion Channels

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The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...
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Non-gated Ion Channels01:24

Non-gated Ion Channels

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Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
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G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

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GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
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Computational Modeling of Retinal Neurons for Visual Prosthesis Research - Fundamental Approaches
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Computational Modeling of Virally-encoded Ion Channel Structure.

Alexander Weissman1, Jeremy Bennett1, Nicole Smith1

  • 1Bates College.

Research Square
|October 27, 2022
PubMed
Summary

Protein structure prediction algorithms accurately modeled rotavirus non-structural protein 4 (NSP4), a key viroporin. These models, despite being trained on non-viral proteins, predicted functional viroporin activity, aiding infectious disease research.

Keywords:
AlphaFoldrotavirusstructure predictiontrRosettaviroporin

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Area of Science:

  • Structural biology
  • Virology
  • Computational biology

Background:

  • Viroporins are viral ion channels crucial for infectious diseases like COVID-19 and rotavirus.
  • Rotavirus non-structural protein 4 (NSP4) acts as a viroporin, disrupting cellular calcium homeostasis and causing severe gastroenteritis.
  • Experimental structure determination of membrane-associated viroporin domains, like NSP4's, is challenging.

Approach:

  • Evaluated AlphaFold2 and trRosetta, protein structure prediction algorithms, for their ability to model full-length rotavirus NSP4.
  • Compared the accuracy of predicted NSP4 structures against experimental data of eukaryotic proteins.
  • Assessed the functional viroporin activity of NSP4 models expressed in E. coli.

Key Points:

  • AlphaFold2 and trRosetta successfully predicted distinct models for the full-length NSP4 protein.
  • Predicted NSP4 structures showed higher accuracy compared to experimental data than previously observed for viroporin structures.
  • Both AlphaFold2 and trRosetta-based NSP4 models exhibited predicted viroporin activity.

Conclusions:

  • Non-viral protein structure prediction algorithms can accurately model viral proteins like NSP4.
  • These computational tools offer a viable approach to studying challenging membrane proteins and viroporins.
  • Accurate NSP4 structure prediction facilitates understanding of rotavirus pathogenesis and potential therapeutic targets.