PDBsum entry 4x3h

Signaling protein

PDB id: 4x3h

Contents

Protein chain

79 a.a.

Ligands

ARG-ILE-PRO-SER-TYR-ARG-TYR-ARG-TYR

Waters ×53

PDB id:

4x3h

Name:

Signaling protein

Title:

Crystal structure of arc n-lobe complexed with stargazin peptide

Structure:

Activity-regulated cytoskeleton-associated protein. Chain: a. Fragment: unp residues 207-277. Synonym: arc/arg3.1,activity-regulated gene 3.1 protein,arg3.1. Engineered: yes. Voltage-dependent calcium channel gamma-2 subunit. Chain: b. Fragment: unp residues 225-233. Synonym: neuronal voltage-gated calcium channel gamma-2 subunit,

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: arc. Expressed in: escherichia coli. Expression_system_taxid: 511693. Mus musculus. Mouse. Organism_taxid: 10090.

Resolution:

2.40Å R-factor: 0.213 R-free: 0.244

Authors:

W.Zhang,M.Ward,D.Leahy,P.Worley

Key ref:

W.Zhang et al. (2015). Structural basis of arc binding to synaptic proteins: implications for cognitive disease. Neuron, 86, 490-500. PubMed id: 25864631 DOI: 10.1016/j.neuron.2015.03.030

Date:

30-Nov-14 Release date: 03-Jun-15

Protein chain

Q63053  (ARC_RAT) -  Activity-regulated cytoskeleton-associated protein from Rattus norvegicus

Seq: 396 a.a.

Struc: 79 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1016/j.neuron.2015.03.030

Neuron 86:490-500 (2015)

PubMed id: 25864631

Structural basis of arc binding to synaptic proteins: implications for cognitive disease.

W.Zhang, J.Wu, M.D.Ward, S.Yang, Y.A.Chuang, M.Xiao, R.Li, D.J.Leahy, P.F.Worley.

ABSTRACT

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 TARPγ2 (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.