Structure of the TRPV1 ion channel determined by electron cryo-microscopy

• Published in: Nature (London) Vol. 504; no. 7478; pp. 107 - 112
• Main Authors: Liao, Maofu, Cao, Erhu, Julius, David, Cheng, Yifan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.12.2013; Nature Publishing Group
• Subjects: 101/28; 631/535/1258/1259; 631/92/269/1153; Animals; Ankyrin Repeat; Cryoelectron Microscopy; Crystal structure; Crystallization; HEK293 Cells; Humanities and Social Sciences; Humans; Ion channels; Membrane proteins; Microscopy; Models, Molecular; multidisciplinary; Observations; Physiological aspects; Protein Structure, Tertiary; Proteins; Rats; Science; Structure; TRPV Cation Channels - chemistry; United States; California
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature12822

Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4 Å resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane segments 5–6 (S5–S6) and the intervening pore loop, which is flanked by S1–S4 voltage-sensor-like domains. TRPV1 has a wide extracellular ‘mouth’ with a short selectivity filter. The conserved ‘TRP domain’ interacts with the S4–S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including amino-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function. A high-resolution electron cryo-microscopy structure of the rat transient receptor potential (TRP) channel TRPV1 in its ‘closed’ state is presented; the overall structure of this ion channel is found to share some common features with voltage-gated ion channels, although several unique, TRP-specific features are also characterized. Open and shut structures for a TRP ion channel Transient receptor potential (TRP) channels are sensors for a wide range of physical and chemical stimuli. In the first of a pair of related papers, Maofu Liao et al . solve the high-resolution electron cryo-microscopy structure of rat TRPV1, the receptor for capsaicin (a pungent agent from chili peppers), in a 'closed' state. The overall structure is fairly similar to that of a voltage-gated ion channel, but there are several structural features unique to TRP channels. In the second paper, Erhu Cao et al . present the structures of rat TRPV1 in the presence of a peptide neurotoxin (resiniferatoxin) and in the presence of capsaicin, yielding structures of activated states of the channel. Comparison of the closed and open structures suggests that TRPV1 has a unique two-gate mechanism of channel activation.