Understanding The Magic Touch (LB101)

Abstract

The Institute of Medicine estimates $635 billion dollars are spent annually on people with chronic pain conditions. One debilitating symptom of these conditions is hypersensitivity to touch, where daily activities can be painful. Few therapeutics to ameliorate mechanical hypersensitivity exist because the mammalian ion channels that sense touch are poorly understood. The mechanosensitive channel of large conductance (MscL) is an ion channel in Mycobacterium tuberculosis which allows bacteria to respond to mechanical stimuli by electrochemical response, regulating membrane ion flow. Research shows structural changes in MscL causes the protein to open, allowing ions into the cell. Key amino acids include hydrophobic residues I14 and V21, creating a constriction at the cytoplasmic surface. R98, K99, K100, E102 and E104 are possibly a ligand binding site, potentially participating in the ion conduction pathway. Residues at the N‐terminus of MscL, K3, F5, E7 and F8, may play a role in sensing membrane stretch. The Laconia SMART (Students Modeling A Research Topic) Team used 3D printing technology to model MscL. Understanding the structure‐function relationships of the MscL channel protein may lead to better comprehension of how human mechanosensitive ion channels, like the Transient Receptor Potential Ankyrin 1, work and lead to a cure for hypersensitivity to touch. Grant Funding Source: Supported by a grant from NIH‐CTSA.