4x3h

Publication Abstract from PubMed

Arc is a cellular immediate-early gene (IEG) that functions at excitatory synapses and is required for learning and memory. We report crystal structures of Arc subdomains that form a bi-lobar architecture remarkably similar to the capsid domain of human immunodeficiency virus (HIV) gag protein. Analysis indicates Arc originated from the Ty3/Gypsy retrotransposon family and was "domesticated" in higher vertebrates for synaptic functions. The Arc N-terminal lobe evolved a unique hydrophobic pocket that mediates intermolecular binding with synaptic proteins as resolved in complexes with TARPgamma2 (Stargazin) and CaMKII peptides and is essential for Arc's synaptic function. A consensus sequence for Arc binding identifies several additional partners that include genes implicated in schizophrenia. Arc N-lobe binding is inhibited by small chemicals suggesting Arc's synaptic action may be druggable. These studies reveal the remarkable evolutionary origin of Arc and provide a structural basis for understanding Arc's contribution to neural plasticity and disease.

Structural basis of arc binding to synaptic proteins: implications for cognitive disease.,Zhang W, Wu J, Ward MD, Yang S, Chuang YA, Xiao M, Li R, Leahy DJ, Worley PF Neuron. 2015 Apr 22;86(2):490-500. doi: 10.1016/j.neuron.2015.03.030. Epub 2015, Apr 9. PMID:25864631^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.