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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
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The Capsid Domain of Arc Changes Its Oligomerization Propensity through Direct Interaction with the NMDA Receptor

Lau Dalby Nielsen1, Christian Parsbæk Pedersen1, Simon Erlendsson2

  • 1Structural Biology and NMR Laboratory and the Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, 2200 Copenhagen N, Denmark.

Structure (London, England : 1993)
|May 14, 2019
PubMed

Insights

Activity-regulated cytoskeleton-associated protein (Arc) forms capsids for mRNA transport. Researchers mapped initial oligomerization changes and found NMDA receptor peptides inhibit this process, suggesting synaptic regulation of Arc function.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Structural Biology

Background:

  • Activity-regulated cytoskeleton-associated protein (Arc) is crucial for synaptic plasticity and scaling in neurons.
  • Arc shares homology with retroviral Gag proteins and can package its own mRNA for intercellular transport.
  • The mechanisms governing Arc capsid assembly and its regulation remain largely unknown.

Purpose of the Study:

  • To investigate the molecular events underlying Arc capsid formation.
  • To elucidate the structural changes involved in Arc oligomerization.
  • To identify potential regulators of Arc capsid assembly and function.

Main Methods:

  • High-resolution structural determination of the Arc capsid domain.
  • Analysis of Arc oligomerization using structural and biochemical approaches.
  • Investigation of the effect of peptide ligands on Arc oligomerization.

Main Results:

  • The Arc capsid domain can form homogeneous oligomers comparable in size to full-length Arc capsids.
  • The N-terminal region of the Arc capsid domain is critical for the initial structural changes during oligomerization.
  • Peptide ligands derived from NMDA receptor subunits inhibit Arc oligomerization.

Conclusions:

  • Arc capsid formation involves transient oligomerization of the capsid domain.
  • Synaptic proteins, such as NMDA receptor subunits, may regulate Arc's mRNA packaging and intercellular transport capabilities.
  • These findings provide insights into the regulation of Arc-mediated synaptic plasticity.
Keywords:
NMR spectroscopyhuman retrotransponprotein structureretroviral capsid

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