Structural properties and peptide ligand binding of the capsid homology domains of human Arc
| Autor: | Petri Kursula, Erik I. Hallin, Clive R. Bramham |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
QH301-705.5 Biophysics Peptide Peptide binding QD415-436 Biochemistry Homology (biology) 03 medical and health sciences 0302 clinical medicine Postsynaptic potential Capsid homology ddc:530 Short linear motif Biology (General) chemistry.chemical_classification Arc (protein) Chemistry Crystal structure Protein interaction Protein dynamics Protein turnover Postsynaptic density 030104 developmental biology Capsid 030220 oncology & carcinogenesis Specificity Phosphorylation Research Article |
| Zdroj: | Biochemistry and biophysics reports 26, 100975 (2021). doi:10.1016/j.bbrep.2021.100975 Biochemistry and Biophysics Reports, Vol 26, Iss, Pp 100975-(2021) Biochemistry and Biophysics Reports |
| DOI: | 10.1101/2020.12.17.423319 |
| Popis: | Biochemistry and biophysics reports 26, 100975 (2021). doi:10.1016/j.bbrep.2021.100975 The activity-regulated cytoskeleton-associated protein (Arc) is important for synaptic plasticity and the normal function of the brain. Arc interacts with neuronal postsynaptic proteins, but the mechanistic details of its function have not been fully established. The C-terminal domain of Arc consists of tandem domains, termed the N- and C-lobe. The N-lobe harbours a peptide binding site, able to bind multiple targets. By measuring the affinity of human Arc towards various peptides from stargazin and guanylate kinase-associated protein (GKAP), we have refined its specificity determinants. We found two sites in the GKAP repeat region that bind to Arc and confirmed these interactions by X-ray crystallography. Phosphorylation of the stargazin peptide did not affect binding affinity but caused changes in thermodynamic parameters. Comparison of the crystal structures of three high-resolution human Arc-peptide complexes identifies three conserved C���H����� interactions at the binding cavity, explaining the sequence specificity of short linear motif binding by Arc. We further characterise central residues of the Arc lobe fold, show the effects of peptide binding on protein dynamics, and identify acyl carrier proteins as structures similar to the Arc lobes. We hypothesise that Arc may affect protein-protein interactions and phase separation at the postsynaptic density, affecting protein turnover and re-modelling of the synapse. The present data on Arc structure and ligand binding will help in further deciphering these processes. Published by Elsevier, Amsterdam [u.a.] |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|