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Conformational plasticity in the selectivity filter of the TRPV2 ion channel.

<div class='caption-title'>Overview of miTRPV2Ca2+ and miTRPV2RTx,Ca2+ and functional characterization of theconstructs</div>
<div class='caption-title'>π-helices in the S4-S5 linker determine the quaternary structure ofsubunits and conformation of the pore helices</div>
<div class='caption-title'>Comparison of miTRPV2EM, miTRPV2Ca2+ and miTRPV2RTx,Ca2+ pores</div>
Zubcevic L, Le S, Yang H, Lee SY
OpenAccess logo Nat Struct Mol Biol 25 405-415 (2018)
Cited: 52 times
EuropePMC logo PMID: 29728656

Abstract

Transient receptor potential vanilloid (TRPV) channels are activated by ligands and heat and are involved in various physiological processes. In contrast to the architecturally related voltage-gated cation channels, TRPV1 and TRPV2 subtypes possess another activation gate at the selectivity filter that can open widely enough to permeate large organic cations. Despite recent structural advances, the mechanism of selectivity filter gating and permeation for both metal ions and large molecules by TRPV1 or TRPV2 is not well known. Here, we determined two crystal structures of rabbit TRPV2 in its Ca2+-bound and resiniferatoxin (RTx)- and Ca2+-bound forms, to 3.9 Å and 3.1 Å, respectively. Notably, our structures show that RTx binding leads to two-fold symmetric opening of the selectivity filter of TRPV2 that is wide enough for large organic cation permeation. Combined with functional characterizations, our studies reveal a structural basis for permeation of Ca2+ and large organic cations in TRPV2.

Reviews - 6bwj mentioned but not cited (6)

  1. Structural insights into the gating mechanisms of TRPV channels. Pumroy RA, Fluck EC, Ahmed T, Moiseenkova-Bell VY. Cell Calcium 87 102168 (2020)
  2. The role of π-helices in TRP channel gating. Zubcevic L, Lee SY. Curr Opin Struct Biol 58 314-323 (2019)
  3. Structural biology of thermoTRPV channels. Yuan P. Cell Calcium 84 102106 (2019)
  4. Ligand-Binding Sites in Vanilloid-Subtype TRP Channels. Yelshanskaya MV, Sobolevsky AI. Front Pharmacol 13 900623 (2022)
  5. TRP ion channels: Proteins with conformational flexibility. López-Romero AE, Hernández-Araiza I, Torres-Quiroz F, Tovar-Y-Romo LB, Islas LD, Rosenbaum T. Channels (Austin) 13 207-226 (2019)
  6. Thermosensory Transient Receptor Potential Ion Channels and Asthma. Kytikova OY, Novgorodtseva TP, Denisenko YK, Naumov DE, Gvozdenko TA, Perelman JM. Biomedicines 9 816 (2021)

Articles - 6bwj mentioned but not cited (9)



Reviews citing this publication (5)

  1. Transient Receptor Potential Channels and Calcium Signaling. Vangeel L, Voets T. Cold Spring Harb Perspect Biol 11 a035048 (2019)
  2. Structural mechanisms of transient receptor potential ion channels. Cao E. J Gen Physiol 152 e201811998 (2020)
  3. The TRPV2 cation channels: from urothelial cancer invasiveness to glioblastoma multiforme interactome signature. Santoni G, Amantini C, Maggi F, Marinelli O, Santoni M, Nabissi M, Morelli MB. Lab Invest 100 186-198 (2020)
  4. High-resolution structures of transient receptor potential vanilloid channels: Unveiling a functionally diverse group of ion channels. van Goor MK, de Jager L, Cheng Y, van der Wijst J. Protein Sci 29 1569-1580 (2020)
  5. [Progress on structural biology of voltage-gated ion channels]. Song F, Guo J. Zhejiang Da Xue Xue Bao Yi Xue Ban 48 25-33 (2019)

Articles citing this publication (32)



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