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Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

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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.
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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.
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Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
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Related Experiment Video

Updated: Jan 13, 2026

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

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PUFA modulation of ASIC3 involves both specific and lipid solvent-like interactions.

Rebecca Roth1, Ramya Bandarupalli2, Robert C Klipp1

  • 1Department of Physiology and Biophysics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Biorxiv : the Preprint Server for Biology
|January 9, 2026
PubMed
Summary
This summary is machine-generated.

Polyunsaturated fatty acids (PUFAs) bind to ASIC3 channels, influencing their function. This study reveals a specific binding site, offering insights into pain and inflammation therapeutics.

Keywords:
Acid-sensing ion channelsArachidonyl GlycineDocosahexaenoic AcidPolyunsaturated Fatty Acids

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Neuroscience

Background:

  • Inflammatory mediators like polyunsaturated fatty acids (PUFAs) are known to modulate acid-sensing ion channel 3 (ASIC3) function.
  • The precise molecular mechanisms underlying PUFA interactions with ASIC3 remain largely undefined.

Purpose of the Study:

  • To elucidate the molecular basis of how docosahexaenoic acid (DHA), a PUFA, interacts with and modulates ASIC3 channel function.
  • To identify the specific binding site and key residues involved in PUFA potentiation of ASIC3.

Main Methods:

  • All-atom molecular dynamics (MD) simulations were employed to visualize DHA accumulation around ASIC3.
  • Electrophysiology experiments were conducted to assess the functional consequences of DHA binding and specific mutations.

Main Results:

  • DHA was observed to accumulate near ASIC3, interacting with a membrane-facing electropositive region on TM1.
  • The carboxylate head group of DHA strongly binds to arginine 63 (R63) in the open channel state, slowing desensitization but not affecting pH sensitivity.
  • Mutation of R63 abolished DHA's effects on desensitization, while effects of N-acyl amino acids (NAAAs) and lysophosphatidylcholines (LPCs) remained unaltered.

Conclusions:

  • This study provides the first detailed characterization of a functional PUFA binding site on ASIC channels.
  • The findings offer novel insights into lipid modulation of ion channel activity and suggest potential therapeutic strategies for pain and inflammation targeting ASIC3-lipid interactions.