TY - JOUR TI - Conserved allosteric pathways for activation of TRPV3 revealed through engineering vanilloid-sensitivity AU - Zhang, Feng AU - Swartz, Kenton Jon AU - Jara-Oseguera, Andres A2 - Csanády, László A2 - Aldrich, Richard VL - 8 PY - 2019 DA - 2019/01/15 SP - e42756 C1 - eLife 2019;8:e42756 DO - 10.7554/eLife.42756 UR - https://doi.org/10.7554/eLife.42756 AB - The Transient Receptor Potential Vanilloid 1 (TRPV) channel is activated by an array of stimuli, including heat and vanilloid compounds. The TRPV1 homologues TRPV2 and TRPV3 are also activated by heat, but sensitivity to vanilloids and many other agonists is not conserved among TRPV subfamily members. It was recently discovered that four mutations in TRPV2 are sufficient to render the channel sensitive to the TRPV1-specific vanilloid agonist resiniferatoxin (RTx). Here, we show that mutation of six residues in TRPV3 corresponding to the vanilloid site in TRPV1 is sufficient to engineer RTx binding. However, robust activation of TRPV3 by RTx requires facilitation of channel opening by introducing mutations in the pore, temperatures > 30°C, or sensitization with another agonist. Our results demonstrate that the energetics of channel activation can determine the apparent sensitivity to a stimulus and suggest that allosteric pathways for activation are conserved in the TRPV family. KW - TRP channel KW - TRPV KW - ion channel gating KW - vanilloid KW - resiniferaroxin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -