Structure of the full-length TRPV2 channel by cryo-EM

Kevin W Huynh,Amrita Samanta,Matthew R Cohen,Jiansen Jiang,Vera Y Moiseenkova-Bell,David T Lodowski,Z Hong Zhou

doi:10.1038/ncomms11130

Abstract

Transient receptor potential (TRP) proteins form a superfamily Ca2+-permeable cation channels regulated by a range of chemical and physical stimuli. Structural analysis of a ‘minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of channel activation by agonists through changes in its outer pore region. Though homologous to TRPV1, other TRPV channels (TRPV2–6) are insensitive to TRPV1 activators including heat and vanilloids. To further understand the structural basis of TRPV channel function, we determined the structure of full-length TRPV2 at ∼5 Å resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two constrictions, one each in the pore-forming upper and lower gates. The agonist-free full-length TRPV2 has wider upper and lower gates compared with closed and agonist-activated TRPV1. We propose these newly revealed TRPV2 structural features contribute to diversity of TRPV channels.

Highlights

Transient receptor potential (TRP) proteins form a superfamily Ca2 þ -permeable cation channels regulated by a range of chemical and physical stimuli
Our previous cryo-electron microscopy (cryo-EM) structure of full-length rat TRPV2 provided a structure at 13.6 Å, which revealed the general architecture of TRPV subfamily members[16]
The position of the apo-TRPV2 S5 helix resembles that of the RTX/DkTx–TRP vanilloid subtype 1 (TRPV1) (Fig. 3b). Together these results suggest that in our cryo-EM structure of the apo-TRPV2 channel, the positions of the ankyrin repeat domain (ARD) and the pore helix differ from both apo-TRPV1 and RTX/DkTx–TRPV1

Summary

Introduction

Transient receptor potential (TRP) proteins form a superfamily Ca2 þ -permeable cation channels regulated by a range of chemical and physical stimuli. A structure of TRPV1 in the presence of capsaicin consists of a closed upper gate and partially open lower gate (Fig. 2c), and may represent an intermediate conformation of the channel[5,6]. Together these results suggest that in our cryo-EM structure of the apo-TRPV2 channel, the positions of the ARDs and the pore helix differ from both apo-TRPV1 and RTX/DkTx–TRPV1.

Results

Conclusion