Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

71-POS Board 71 Probing the Role of the S1-S4 Ligand-sensing Domain in TRPV1 Gating Minjoo Kim, Nicholas J. Sisco, Jacob K. Hilton, Wade D. Van Horn . Arizona State Univestity, Tempe, AZ, USA.

The human TRPV1 ion channel is involved in diverse physiological processes and has been implicated in a variety of pathophysiologies. Presumably to fulfill disparate functional roles, the channel is modulated by various types of stimuli, including temperature, chemical ligands, pH, voltage, and regulatory proteins. A number of previous studies have identified the S1-S4 membrane ligand-sensing domain as central to vanilloid chemical-based TRPV1 agonism. In an effort to experimentally identify the binding site at the molecular level, the isolated human TRPV1 ligand-sensing domain (hV1-SD) was expressed and purified. NMR characterization of this domain has led to resonance assignment which allows for binding studies that precisely identify the specific residues and atoms key to vanilloid binding. A comparative binding study of the hV1-SD with the canonical vanilloid, capsaicin will be discussed. Additionally, the role of this domain in phosphoinositide lipid binding and its structural and thermodynamic response to changes in temperature will also be highlighted.

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