Extensions of PSD‐95/discs large/ZO‐1 (PDZ) domains influence lipid binding and membrane targeting of syntenin‐1

Abstract

a b s t r a c tSyntenin-1 is a PDZ protein involved in receptor recycling and clustering. Its two PDZ domains interact with various receptors and phosphoinositides, and are flanked by N-and C-terminal regions. Here, we report the identification of an autoinhibitory peptide stretch in the N-terminus that might be regulated by phosphorylation. We further establish that basic residues in the C-terminal region mediate electrostatic interactions with reconstituted liposomes and contribute to the plasma membrane targeting. Our study adds new components to the multi-dentate membrane targeting mechanism and highlights the role of N-and C-terminal PDZ extensions in the regulation of syntenin-1 plasma membrane localization. Structured summary of protein interactions:PDZ1-PDZ2 and peptide bind by fluorescence technology (View Interaction: 1, 2, 3, 4).

Ligand-Induced Dynamic Changes in Extended PDZ Domains from NHERF1

“…Owing to high sequence homology between canonical PDZ domains, frequently the presence variable structures at the termini are overlooked. Our results substantiate an emerging theme that the sequence and structural propensity beyond the canonical PDZ domains are remarkably diverse and critical for mediating PDZ function 4; 61; 62; 63; 64; 65 .…”

A Structural Portrait of the PDZ Domain Family

“…However, we believe that further research will be required to elucidate the molecular paths PDZ domains may take to evolve divergent binding specificities [11,27]. Furthermore, some PDZ domains can bind productively to internal regions of proteins [3,29,30] but only a few structures are available for such interactions and these binding mechanisms are poorly understood [15,30]. Finally, the recent finding that many PDZ domains may interact with membrane phospholipids raises new questions about how these interactions are structurally accommodated and what impact the lipid ligand may have on peptide binding [31][32][33].…”

Extracellular matrix component signaling in cancer

“…Recent work also suggests that PDZ interactions have relevance to trafficking, perhaps routing proteoglycans to the cell surface [183]. In addition, however, there is interesting evidence to suggest that syntenin/syndecan in conjunction with the syntenin-binding protein ALIX is involved in, or can enhance, exosome production [184].…”