Exploring the Conformational Impact of Glycine Receptor TM1-2 Mutations Through Coarse-Grained Analysis and Atomistic Simulations.

ABSTRACT: Pentameric ligand-gated ion channels (PLGICs) are a family of proteins that convert chemical signals into ion fluxes through cellular membranes. Their structures are highly conserved across all kingdoms from bacteria to eukaryotes. Beyond their classical roles in neurotransmission and neurological disorders, PLGICs have been recently related to cell proliferation and cancer. Here, we focus on the best characterized eukaryotic channel, the glycine receptor (GlyR), to investigate its mutational patterns in genomic-wide tumor screens and compare them with mutations linked to hyperekplexia (HPX), a Mendelian neuromotor disease that disrupts glycinergic currents. Our analysis highlights that cancer mutations significantly accumulate across TM1 and TM2, partially overlapping with HPX changes. Ba

SUBMITTER: Mhashal AR 

PROVIDER: S-EPMC9275627 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature