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Intramolecular domain dynamics regulate synaptic MAGUK protein interactions.
- Source :
-
ELife [Elife] 2019 Mar 13; Vol. 8. Date of Electronic Publication: 2019 Mar 13. - Publication Year :
- 2019
-
Abstract
- PSD-95 MAGUK family scaffold proteins are multi-domain organisers of synaptic transmission that contain three PDZ domains followed by an SH3-GK domain tandem. This domain architecture allows coordinated assembly of protein complexes composed of neurotransmitter receptors, synaptic adhesion molecules and downstream signalling effectors. Here we show that binding of monomeric CRIPT-derived PDZ <subscript>3</subscript> ligands to the third PDZ domain of PSD-95 induces functional changes in the intramolecular SH3-GK domain assembly that influence subsequent homotypic and heterotypic complex formation. We identify PSD-95 interactors that differentially bind to the SH3-GK domain tandem depending on its conformational state. Among these interactors, we further establish the heterotrimeric G protein subunit Gnb5 as a PSD-95 complex partner at dendritic spines of rat hippocampal neurons. The PSD-95 GK domain binds to Gnb5, and this interaction is triggered by CRIPT-derived PDZ <subscript>3</subscript> ligands binding to the third PDZ domain of PSD-95, unraveling a hierarchical binding mechanism of PSD-95 complex formation.<br />Competing Interests: NR, BK, SK, MW, CF, SS No competing interests declared<br /> (© 2019, Rademacher et al.)
- Subjects :
- Animals
COS Cells
Chlorocebus aethiops
HEK293 Cells
Hippocampus cytology
Humans
Protein Binding
Protein Conformation
Protein Domains
Adaptor Proteins, Signal Transducing metabolism
Disks Large Homolog 4 Protein chemistry
Disks Large Homolog 4 Protein metabolism
GTP-Binding Protein beta Subunits metabolism
Protein Multimerization
Synapses chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 30864948
- Full Text :
- https://doi.org/10.7554/eLife.41299