Coarse Architecture of the Transient Receptor Potential Vanilloid 1 (TRPV1) Ion Channel Determined by Fluorescence Resonance Energy Transfer

Rosa, Víctor De la; Rangel‐Yescas, Gisela E.; Ladrón‐de‐Guevara, Ernesto; Rosenbaum, Tamara; Islas, León D

doi:10.1074/jbc.m113.479618

Cited by 41 publications

(43 citation statements)

References 46 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The utilization of a membrane-tethered peptide in our in vivo experiments is supported by recent FRET analysis that determined the proximity of TRPV1 terminal domains to the plasma membrane (43). In this study the authors were able to show that the C terminus was closer to the plasma membrane than the N terminus, which suggests that, once incorporated into the membrane, our palmitoylated TRPV1 peptide would likely have access to the C terminus to disrupt subunit assembly.…”

Section: Discussionsupporting

confidence: 66%

Targeting the Transient Receptor Potential Vanilloid Type 1 (TRPV1) Assembly Domain Attenuates Inflammation-induced Hypersensitivity

Flynn

Chapman

Iftinca

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Assembly of TRPV1 subunits forms functional channels that transduce noxious stimuli. Results: We identified a region of the TRPV1 C terminus that mediates subunit assembly and used a disrupting peptide to block association. Conclusion: A short C-terminal motif enables subunit association. Disrupting assembly of TRPV1 subunits attenuates inflammatory hyperalgesia. Significance: TRPV1 subunit association could be targeted for pain relief.

show abstract

Section: Discussionsupporting

confidence: 66%

Targeting the Transient Receptor Potential Vanilloid Type 1 (TRPV1) Assembly Domain Attenuates Inflammation-induced Hypersensitivity

Flynn

Chapman

Iftinca

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…7 A, dashed black trace), L-ANAP (black trace) and YFP (blue trace). FRET between YFP at the N terminus of TRPV1 and CFP at the C terminus of TRPV1 has been previously reported (De-la-Rosa et al, 2013). Our data suggest that, of the three positions into which we incorporated L-ANAP, Q169 may be the closest to YFP fused to the C terminus.…”

Section: Expression Of L-anap-incorporated Trpv1 Constructs As Functisupporting

confidence: 52%

Measuring distances between TRPV1 and the plasma membrane using a noncanonical amino acid and transition metal ion FRET

Zagotta¹,

Gordon²,

Senning³

et al. 2016

J Cell Biol

View full text Add to dashboard Cite

Despite recent advances, the structure and dynamics of membrane proteins in cell membranes remain elusive. We implemented transition metal ion fluorescence resonance energy transfer (tmFRET) to measure distances between sites on the N-terminal ankyrin repeat domains (ARDs) of the pain-transducing ion channel TRPV1 and the intracellular surface of the plasma membrane. To preserve the native context, we used unroofed cells, and to specifically label sites in TRPV1, we incorporated a fluorescent, noncanonical amino acid, L-ANAP. A metal chelating lipid was used to decorate the plasma membrane with high-density/high-affinity metal-binding sites. The fluorescence resonance energy transfer (FRET) efficiencies between L-ANAP in TRPV1 and Co 2+ bound to the plasma membrane were consistent with the arrangement of the ARDs in recent cryoelectron microscopy structures of TRPV1. No change in tmFRET was observed with the TRPV1 agonist capsaicin. These results demonstrate the power of tmFRET for measuring structure and rearrangements of membrane proteins relative to the cell membrane.

show abstract

“…The structure of the ankyrin repeat domain has been determined with high resolution using x-ray crystallography (Lishko et al 2007), and the structure of the complete channel has been resolved to 19 Å with singleparticle electron cryo-microscopy (Moiseenkova-Bell et al 2008). The compact structure obtained with electron cryo-microscopy is largely consistent with the channel architecture determined by FRET measurements (De-la-Rosa et al 2013). A pore-forming loop containing an outer pore 'turret', a pore helix and a selectivity filter is located between TM segments 5 and 6 (Venkatachalam and Montell 2007;Latorre et al 2009).…”

Section: Structure and Functionmentioning

confidence: 76%

Trpv1

Bevan¹,

Quallo²,

Andersson³

2014

Handbook of Experimental Pharmacology

154

125

View full text Add to dashboard Cite

TRPV1 is a well-characterised channel expressed by a subset of peripheral sensory neurons involved in pain sensation and also at a number of other neuronal and non-neuronal sites in the mammalian body. Functionally, TRPV1 acts as a sensor for noxious heat (greater than ~42 °C). It can also be activated by some endogenous lipid-derived molecules, acidic solutions (pH < 6.5) and some pungent chemicals and food ingredients such as capsaicin, as well as by toxins such as resiniferatoxin and vanillotoxins. Structurally, TRPV1 subunits have six transmembrane (TM) domains with intracellular N- (containing 6 ankyrin-like repeats) and C-termini and a pore region between TM5 and TM6 containing sites that are important for channel activation and ion selectivity. The N- and C- termini have residues and regions that are sites for phosphorylation/dephosphorylation and PI(4,5)P2 binding, which regulate TRPV1 sensitivity and membrane insertion. The channel has several interacting proteins, some of which (e.g. AKAP79/150) are important for TRPV1 phosphorylation. Four TRPV1 subunits form a non-selective, outwardly rectifying ion channel permeable to monovalent and divalent cations with a single-channel conductance of 50-100 pS. TRPV1 channel kinetics reveal multiple open and closed states, and several models for channel activation by voltage, ligand binding and temperature have been proposed. Studies with TRPV1 agonists and antagonists and Trpv1 (-/-) mice have suggested a role for TRPV1 in pain, thermoregulation and osmoregulation, as well as in cough and overactive bladder. TRPV1 antagonists have advanced to clinical trials where findings of drug-induced hyperthermia and loss of heat sensitivity have raised questions about the viability of this therapeutic approach.

show abstract

Coarse Architecture of the Transient Receptor Potential Vanilloid 1 (TRPV1) Ion Channel Determined by Fluorescence Resonance Energy Transfer

Cited by 41 publications

References 46 publications

Targeting the Transient Receptor Potential Vanilloid Type 1 (TRPV1) Assembly Domain Attenuates Inflammation-induced Hypersensitivity

Targeting the Transient Receptor Potential Vanilloid Type 1 (TRPV1) Assembly Domain Attenuates Inflammation-induced Hypersensitivity

Measuring distances between TRPV1 and the plasma membrane using a noncanonical amino acid and transition metal ion FRET

Trpv1

Contact Info

Product

Resources

About