4x3i
From Proteopedia
The crystal structure of Arc N-lobe complexed with CAMK2A fragment
Structural highlights
FunctionARC_RAT Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the stress fiber dynamics and cell migration (By similarity). Required for consolidation of synaptic plasticity as well as formation of long-term memory. Regulates endocytosis of AMPA receptors in response to synaptic activity. Required for homeostatic synaptic scaling of AMPA receptors.[1] [2] Publication Abstract from PubMedArc 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. References
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