Abstract
The activity-regulated cytoskeleton-associated protein, Arc, is highly expressed in neuronal dendrites and is involved in synaptic scaling and plasticity. Arc exhibits homology to the capsid-forming Gag proteins from retroviruses and can encapsulate its own mRNA and transport it to neighboring neurons. However, the molecular events that lead to the assembly of Arc capsids and how the capsid formation is regulated are not known. Here we show that the capsid domain of Arc may transiently form homogeneous oligomers of similar size as capsids formed by full-length Arc. We determined a high-resolution structure of the monomeric Arc capsid domain and mapped the initial structural change in the oligomerization process to the N-terminal part of the capsid domain. Peptide ligands from the NMDA receptor subunits inhibit oligomerization, which suggests that Arc's ability to transfer mRNA between cells may be regulated by protein-protein interactions at the synapse.
Keywords:
NMR spectroscopy; human retrotranspon; protein structure; retroviral capsid.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Capsid Proteins / chemistry*
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Capsid Proteins / genetics
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Capsid Proteins / metabolism
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Cloning, Molecular
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Crystallography, X-Ray
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Cytoskeletal Proteins / chemistry*
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Gene Expression
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Genetic Vectors / chemistry
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Genetic Vectors / metabolism
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Humans
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Kinetics
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Models, Molecular
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Nerve Tissue Proteins / chemistry*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neurons / chemistry
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Neurons / metabolism
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Protein Binding
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Protein Conformation, alpha-Helical
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Protein Conformation, beta-Strand
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Protein Interaction Domains and Motifs
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Protein Multimerization
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Rats
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Receptors, N-Methyl-D-Aspartate / chemistry*
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Receptors, N-Methyl-D-Aspartate / genetics
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Receptors, N-Methyl-D-Aspartate / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
Substances
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Capsid Proteins
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Cytoskeletal Proteins
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NR2B NMDA receptor
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Nerve Tissue Proteins
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Receptors, N-Methyl-D-Aspartate
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Recombinant Proteins
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activity regulated cytoskeletal-associated protein
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N-methyl D-aspartate receptor subtype 2A