Structure of TRPV1 channel revealed by electron cryomicroscopy.
The transient receptor potential (TRP) family of ion channels participate in many signaling pathways. TRPV1 functions as a molecular integrator of noxious stimuli, including heat, low pH, and chemical ligands. Here, we report the 3D structure of full-length rat TRPV1 channel expressed in the yeast Saccharomyces cerevisiae and purified by immunoaffinity chromatography. We demonstrate that the recombinant purified TRPV1 channel retains its structural and functional integrity and is suitable for structural analysis. The 19-A structure of TRPV1 determined by using single-particle electron cryomicroscopy exhibits fourfold symmetry and comprises two distinct regions: a large open basket-like domain, likely corresponding to the cytoplasmic N- and C-terminal portions, and a more compact domain, corresponding to the transmembrane portion. The assignment of transmembrane and cytoplasmic regions was supported by fitting crystal structures of the structurally homologous Kv1.2 channel and isolated TRPV1 ankyrin repeats into the TRPV1 structure.
Moiseenkova-Bell
Vera Y
VY
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Stanciu
Lia A
LA
Serysheva
Irina I
II
Tobe
Ben J
BJ
Wensel
Theodore G
TG
D000818:Animals; D017089:Ankyrin Repeat; D002462:Cell Membrane / Q000737:chemistry; D020285:Cryoelectron Microscopy / Q000379:methods; D003461:Crystallography; D003593:Cytoplasm / Q000737:chemistry; D021621:Imaging, Three-Dimensional; D051663:Kv1.2 Potassium Channel / Q000737:chemistry; D011487:Protein Conformation; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D012441:Saccharomyces cerevisiae / Q000235:genetics; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification
D051663:Kv1.2 Potassium Channel; D011994:Recombinant Proteins; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat