6s7y
dARC1 capsid domain dimer, hexagonal form at 2.3 Angstrom
Structural highlights
FunctionARC1_DROME Master regulator of synaptic plasticity that self-assembles into virion-like capsids that encapsulate RNAs and mediate intercellular RNA transfer from motorneurons to muscles (PubMed:29328915). Arc1 protein is released from motorneurons in extracellular vesicles that mediate the transfer of Arc1 mRNA into muscle cells, where Arc1 mRNA can undergo activity-dependent translation (PubMed:29328915). Intercellular transfer od Arc1 mRNA is required for synaptic plasticity at the neuromuscular junction (PubMed:29328915). May play a role in energy balance: required for regulation of body fat by a specific population of brain neurons, named E347, that are necessary and sufficient for proper body fat storage (PubMed:26209258).[1] [2] Publication Abstract from PubMedThe tetrapod neuronal protein ARC and its Drosophila melanogaster homolog, dARC1, have important but differing roles in neuronal development. Both are thought to originate through exaptation of ancient Ty3/Gypsy retrotransposon Gag, with their novel function relying on an original capacity for self-assembly and encapsidation of nucleic acids. Here, we present the crystal structure of dARC1 CA and examine the relationship between dARC1, mammalian ARC, and the CA protein of circulating retroviruses. We show that while the overall architecture is highly related to that of orthoretroviral and spumaretroviral CA, there are substantial deviations in both amino- and carboxyl-terminal domains, potentially affecting recruitment of partner proteins and particle assembly. The degree of sequence and structural divergence suggests that Ty3/Gypsy Gag has been exapted on two separate occasions and that, although mammalian ARC and dARC1 share functional similarity, the structures have undergone different adaptations after appropriation into the tetrapod and insect genomes. Structure of Drosophila melanogaster ARC1 reveals a repurposed molecule with characteristics of retroviral Gag.,Cottee MA, Letham SC, Young GR, Stoye JP, Taylor IA Sci Adv. 2020 Jan 1;6(1):eaay6354. doi: 10.1126/sciadv.aay6354. eCollection 2020 , Jan. PMID:31911950[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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