Download MendeleyThe Capsid Domain of Arc Changes Its Oligomerization Propensity through Direct Interaction with the NMDA Receptor.
Nielsen, L.D., Pedersen, C.P., Erlendsson, S., Teilum, K.(2019) Structure 27: 1071-1081.e5
- PubMed: 31080121
- DOI: https://doi.org/10.1016/j.str.2019.04.001
- Primary Citation of Related Structures:
6GSE - PubMed 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.
Organizational Affiliation:
Structural Biology and NMR Laboratory and the Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, 2200 Copenhagen N, Denmark.
