Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Thursday Speaker Abstracts

Structural Basis of the TRPV5 Channel Modulation Revealed by Cryo-EM Taylor Hughes Case Western Reserve University, Cleveland, OH, USA.

Nephrolithiasis, commonly known as kidney stones, is a common disease that affects approximately 30 million Americans annually. One of the most critical risk factors is hypercalciuria, or high levels of Ca 2+ in urine. TRPV5 is a highly Ca 2+ selective, kidney specific TRP channel that plays a critical role in systemic calcium homeostasis. Loss or dysfunction of TRPV5 has been shown to severely increase urine Ca 2+ levels and the occurrence of kidney stones. To this end, we have determined TRPV5 structures in apo, econazole-inhibited and lipid- modulated states by Cryo-EM. The inhibited state TRPV5 channel structure enabled us to identify the econazole-binding site and reveal an aromatic gate that occludes the Ca 2+ permeation through the channel. Apo- and lipid-bound TRPV5 structures uncovered the endogenous lipid modulation mechanism of this kidney specific channel and we are pursuing this project further to understand how mutations in this channel affect its gating and lead to kidney stone formation.

Structure of Membrane Transporters Nancy Carrasco Yale University, New Haven, CT, USA No Abstract

Gating and Ligand Modulation in Potassium Channels Crina Nimigean Cornell University, Ithaca, NY, USA No Abstract

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