An intramolecular interaction between Src homology 3 domain and guanylate kinase-like domain required for channel clustering by postsynaptic density-95/SAP90

Citation
Hw. Shin et al., An intramolecular interaction between Src homology 3 domain and guanylate kinase-like domain required for channel clustering by postsynaptic density-95/SAP90, J NEUROSC, 20(10), 2000, pp. 3580-3587
Citations number
44
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
02706474 → ACNP
Volume
20
Issue
10
Year of publication
2000
Pages
3580 - 3587
Database
ISI
SICI code
0270-6474(20000515)20:10<3580:AIIBSH>2.0.ZU;2-R
Abstract
Members of the postsynaptic density-95 (PSD-95)/SAP90 family of membrane-as sociated guanylate kinase (MAGUK) proteins function as multimodular scaffol ds that organize protein-signaling complexes at neuronal synapses. MAGUK pr oteins contain PDZ, Src homology 3 (SH3), and guanylate kinase (GK)-like do mains, all of which can function as sites for specific protein-protein inte ractions. We report here a direct protein-protein interaction between the S H3 domain and the GK region in the PSD-95 family of MAGUKs. The SH3 domain of the PSD-95 family appears to have an atypical binding specificity, becau se the classical SH3 binding (-P-X-X-P-) motif is absent from the GK domain . Although SH3-GK binding can occur in either an intramolecular or intermol ecular manner, the intramolecular mode is preferred, possibly because of ad ditional tertiary interactions available when the SH3 and GK domains are ad jacent in the same polypeptide. Mutations disrupting the intramolecular SH3 -GK interaction do not interfere with PSD-95 association with the K+ channe l Kv1.4 or with the GK domain-binding protein GKAP. The same mutations, how ever, inhibit the clustering of Kv1.4 by PSD-95, suggesting that the intram olecular SH3-GK interaction may modulate the clustering activity of PSD-95.