SSRP Abstract

Board 1: Characterizing the M3-M4 Loop of the Glycine Receptors Potential to Transverse the Membrane

Student Scientist: Erin Pohlman ’23
Research Mentor: Kayce Tomcho (OWU Department of Chemistry)

Proteins play an important role in our bodies which have parts with certain functions linked to their appearance; their structure. Like baking a cake, each ingredient has a specific function to yield the best result. If you incorrectly add or omit an ingredient then the cake won’t look right, and a baker needs to know what caused the problem. The glycine receptor (GlyR) can lead to different illness if a mutation to the receptor occurs. Our study focuses on a certain piece of the receptor to better understand how that particular “ingredient” impacts its appearance — its structure — which gives more insight into its function and therefore, illnesses linked to the receptor can be better treated.

The glycine receptor (GlyR) is part of a family of pentameric ligand-gated ion channels (pLGICs) that allows chloride ion influx which hyperpolarizes the cell. A recent study by Tomcho et al. using crosslinking mass spectrometry and single, systematic cysteine mutations in resting, open and desensitized states, indicated that the intracellular M3-M4 loop of GlyR is dynamic, which is consistent with previous literature findings. This study also suggests the ability of the loop to transverse the membrane similar to cell penetrating peptides (CPPs). CPPs are peptides that facilitate cellular intake and uptake by passing through the membrane and consist of basic or amphipathic chains of 5-30 amino acids. The M3-M4 loop is rich in lysine and arginine residues and thus, resembles the sequences of CPPs found in vivo. This study aims to characterize the interactions between the M3-M4 loop and a native-like membrane bilayer, both as truncated segments and as the whole nearly 70 residues in the loop. Advancing the understanding of the structure-function relationship is essential to improving therapeutics to treat conditions linked to GlyR.