Stapled Voltage-Gated Calcium Channel (Ca_V) α-Interaction Domain (AID) Peptides Act As Selective Protein-Protein Interaction Inhibitors of Ca_V Function.

ABSTRACT: For many voltage-gated ion channels (VGICs), creation of a properly functioning ion channel requires the formation of specific protein-protein interactions between the transmembrane pore-forming subunits and cystoplasmic accessory subunits. Despite the importance of such protein-protein interactions in VGIC function and assembly, their potential as sites for VGIC modulator development has been largely overlooked. Here, we develop meta-xylyl (m-xylyl) stapled peptides that target a prototypic VGIC high affinity protein-protein interaction, the interaction between the voltage-gated calcium channel (Ca_V) pore-forming subunit α-interaction domain (AID) and cytoplasmic β-subunit (Ca_Vβ). We show using circular dichroism spectroscopy, X-ray crystallography, and isothermal ti

SUBMITTER: Findeisen F 

PROVIDER: S-EPMC5481814 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature