Abstract
The transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel responsive to various stimuli including cell swelling, warm temperatures (27-35 degrees C), and chemical compounds such as phorbol ester derivatives. Here we report the three-dimensional structure of full-length rat TRPV4 purified from baculovirus-infected Sf9 cells. Hexahistidine-tagged rat TRPV4 (His-rTRPV4) was solubilized with detergent and purified through affinity chromatography and size-exclusion chromatography. Chemical cross-linking analysis revealed that detergent-solubilized His-rTRPV4 was a tetramer. The 3.5-nm structure of rat TRPV4 was determined by cryoelectron microscopy using single-particle reconstruction from Zernike phase-contrast images. The overall structure comprises two distinct regions; a larger dense component, likely corresponding to the cytoplasmic N- and C-terminal regions, and a smaller component corresponding to the transmembrane region.
Highlights
transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel that was originally identified as an osmosensor that detects hypotonic stimuli (6 –9)
X-ray crystallography of fragments of the cytoplasmic region has been employed to understand its regulatory mechanism at atomic resolution (26 –31), and electron microscopy (EM) of full-length Transient receptor potential (TRP) channels has been used to observe the entire structure of channel molecules
The three-dimensional model consists of two components; a larger dense part, likely corresponding to the cytoplasmic N- and C-terminal regions, and a smaller component corresponding to transmembrane region
Summary
TRPV4 is a non-selective cation channel that was originally identified as an osmosensor that detects hypotonic stimuli (6 –9). The structure of TRPV4 is predicted to have a transmembrane region homologous to the 6TM tetrameric cation channels and ankyrin repeat domains (ARDs) in the N-terminal sequence [6]. Three-dimensional Reconstruction of TRPV4 Channel cryo-EM structure of TRPC3 at 1.5-nm of resolution showed a large volume with a mesh-like structure.
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