35 / 119
Emerging Concepts in Ion Channel Biophysics
Thursday Speaker Abstracts
30
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