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PDBsum entry 2pnn
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Transport protein
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PDB id
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2pnn
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* Residue conservation analysis
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PDB id:
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Transport protein
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Title:
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Crystal structure of the ankyrin repeat domain of trpv1
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Structure:
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Transient receptor potential cation channel subfamily v member 1. Chain: a. Fragment: ankyrin repeat domain. Synonym: trpv1, osm-9-like trp channel 1, otrpc1, vanilloid receptor 1, vanilloid receptor type 1-like, capsaicin receptor. Engineered: yes
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Source:
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Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: trpv1, vr1, vr1l. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
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Resolution:
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2.70Å
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R-factor:
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0.202
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R-free:
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0.248
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Authors:
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X.Jin,R.Gaudet
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Key ref:
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P.V.Lishko
et al.
(2007).
The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity.
Neuron,
54,
905-918.
PubMed id:
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Date:
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24-Apr-07
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Release date:
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03-Jul-07
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PROCHECK
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Headers
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References
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O35433
(TRPV1_RAT) -
Transient receptor potential cation channel subfamily V member 1 from Rattus norvegicus
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Seq:
Struc:
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838 a.a.
248 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Neuron
54:905-918
(2007)
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PubMed id:
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The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity.
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P.V.Lishko,
E.Procko,
X.Jin,
C.B.Phelps,
R.Gaudet.
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ABSTRACT
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TRPV1 plays a key role in nociception, as it is activated by heat, low pH, and
ligands such as capsaicin, leading to a burning pain sensation. We describe the
structure of the cytosolic ankyrin repeat domain (ARD) of TRPV1 and identify a
multiligand-binding site important in regulating channel sensitivity within the
TRPV1-ARD. The structure reveals a binding site that accommodates triphosphate
nucleotides such as ATP, and biochemical studies demonstrate that calmodulin
binds the same site. Electrophysiology experiments show that either ATP or PIP2
prevent desensitization to repeated applications of capsaicin, i.e.,
tachyphylaxis, while calmodulin plays an opposing role and is necessary for
tachyphylaxis. Mutations in the TRPV1-ARD binding site eliminate tachyphylaxis.
We present a model for the calcium-dependent regulation of TRPV1 via competitive
interactions of ATP and calmodulin at the TRPV1-ARD-binding site and discuss its
relationship to the C-terminal region previously implicated in interactions with
PIP2 and calmodulin.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.Chakrabarti,
B.K.Jha,
and
R.H.Silverman
(2011).
New insights into the role of RNase L in innate immunity.
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J Interferon Cytokine Res,
31,
49-57.
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E.D.Por,
B.K.Samelson,
S.Belugin,
A.N.Akopian,
J.D.Scott,
and
N.A.Jeske
(2010).
PP2B/calcineurin-mediated desensitization of TRPV1 does not require AKAP150.
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Biochem J,
432,
549-556.
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G.Landouré,
A.A.Zdebik,
T.L.Martinez,
B.G.Burnett,
H.C.Stanescu,
H.Inada,
Y.Shi,
A.A.Taye,
L.Kong,
C.H.Munns,
S.S.Choo,
C.B.Phelps,
R.Paudel,
H.Houlden,
C.L.Ludlow,
M.J.Caterina,
R.Gaudet,
R.Kleta,
K.H.Fischbeck,
and
C.J.Sumner
(2010).
Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.
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Nat Genet,
42,
170-174.
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PDB codes:
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I.Díaz-Laviada
(2010).
Effect of capsaicin on prostate cancer cells.
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Future Oncol,
6,
1545-1550.
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J.E.Linley,
K.Rose,
L.Ooi,
and
N.Gamper
(2010).
Understanding inflammatory pain: ion channels contributing to acute and chronic nociception.
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Pflugers Arch,
459,
657-669.
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J.Mercado,
A.Gordon-Shaag,
W.N.Zagotta,
and
S.E.Gordon
(2010).
Ca2+-dependent desensitization of TRPV2 channels is mediated by hydrolysis of phosphatidylinositol 4,5-bisphosphate.
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J Neurosci,
30,
13338-13347.
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M.Auer-Grumbach,
A.Olschewski,
L.Papić,
H.Kremer,
M.E.McEntagart,
S.Uhrig,
C.Fischer,
E.Fröhlich,
Z.Bálint,
B.Tang,
H.Strohmaier,
H.Lochmüller,
B.Schlotter-Weigel,
J.Senderek,
A.Krebs,
K.J.Dick,
R.Petty,
C.Longman,
N.E.Anderson,
G.W.Padberg,
H.J.Schelhaas,
C.M.van Ravenswaaij-Arts,
T.R.Pieber,
A.H.Crosby,
and
C.Guelly
(2010).
Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.
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Nat Genet,
42,
160-164.
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N.A.Sowa,
S.E.Street,
P.Vihko,
and
M.J.Zylka
(2010).
Prostatic acid phosphatase reduces thermal sensitivity and chronic pain sensitization by depleting phosphatidylinositol 4,5-bisphosphate.
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J Neurosci,
30,
10282-10293.
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R.Strotmann,
M.Semtner,
F.Kepura,
T.D.Plant,
and
T.Schöneberg
(2010).
Interdomain interactions control Ca2+-dependent potentiation in the cation channel TRPV4.
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PLoS One,
5,
e10580.
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V.Lyall,
T.H.Phan,
Z.Ren,
S.Mummalaneni,
P.Melone,
S.Mahavadi,
K.S.Murthy,
and
J.A.DeSimone
(2010).
Regulation of the putative TRPV1t salt taste receptor by phosphatidylinositol 4,5-bisphosphate.
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J Neurophysiol,
103,
1337-1349.
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A.Dhaka,
V.Uzzell,
A.E.Dubin,
J.Mathur,
M.Petrus,
M.Bandell,
and
A.Patapoutian
(2009).
TRPV1 is activated by both acidic and basic pH.
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J Neurosci,
29,
153-158.
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A.Malkia,
M.Pertusa,
G.Fernández-Ballester,
A.Ferrer-Montiel,
and
F.Viana
(2009).
Differential role of the menthol-binding residue Y745 in the antagonism of thermally gated TRPM8 channels.
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Mol Pain,
5,
62.
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B.Thyagarajan,
B.S.Benn,
S.Christakos,
and
T.Rohacs
(2009).
Phospholipase C-mediated regulation of transient receptor potential vanilloid 6 channels: implications in active intestinal Ca2+ transport.
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Mol Pharmacol,
75,
608-616.
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H.Salazar,
A.Jara-Oseguera,
E.Hernández-García,
I.Llorente,
I.I.Arias-Olguín,
M.Soriano-García,
L.D.Islas,
and
T.Rosenbaum
(2009).
Structural determinants of gating in the TRPV1 channel.
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Nat Struct Mol Biol,
16,
704-710.
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K.Y.Kwan,
J.M.Glazer,
D.P.Corey,
F.L.Rice,
and
C.L.Stucky
(2009).
TRPA1 modulates mechanotransduction in cutaneous sensory neurons.
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J Neurosci,
29,
4808-4819.
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M.S.Riedl,
P.D.Braun,
K.F.Kitto,
S.A.Roiko,
L.B.Anderson,
C.N.Honda,
C.A.Fairbanks,
and
L.Vulchanova
(2009).
Proteomic analysis uncovers novel actions of the neurosecretory protein VGF in nociceptive processing.
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J Neurosci,
29,
13377-13388.
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N.A.Jeske,
A.M.Patwardhan,
N.B.Ruparel,
A.N.Akopian,
M.S.Shapiro,
and
M.A.Henry
(2009).
A-kinase anchoring protein 150 controls protein kinase C-mediated phosphorylation and sensitization of TRPV1.
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Pain,
146,
301-307.
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R.Gaudet
(2009).
Divide and conquer: high resolution structural information on TRP channel fragments.
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J Gen Physiol,
133,
231-237.
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R.L.Daniels,
Y.Takashima,
and
D.D.McKemy
(2009).
Activity of the neuronal cold sensor TRPM8 is regulated by phospholipase C via the phospholipid phosphoinositol 4,5-bisphosphate.
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J Biol Chem,
284,
1570-1582.
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R.Latorre,
C.Zaelzer,
and
S.Brauchi
(2009).
Structure-functional intimacies of transient receptor potential channels.
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Q Rev Biophys,
42,
201-246.
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S.Gallego-Sandín,
A.Rodríguez-García,
M.T.Alonso,
and
J.García-Sancho
(2009).
The endoplasmic reticulum of dorsal root ganglion neurons contains functional TRPV1 channels.
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J Biol Chem,
284,
32591-32601.
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T.Rohacs
(2009).
Phosphoinositide regulation of non-canonical transient receptor potential channels.
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Cell Calcium,
45,
554-565.
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V.Y.Moiseenkova-Bell,
and
T.G.Wensel
(2009).
Hot on the trail of TRP channel structure.
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J Gen Physiol,
133,
239-244.
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A.Garcia-Elias,
I.M.Lorenzo,
R.Vicente,
and
M.A.Valverde
(2008).
IP3 Receptor Binds to and Sensitizes TRPV4 Channel to Osmotic Stimuli via a Calmodulin-binding Site.
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J Biol Chem,
283,
31284-31288.
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A.Jara-Oseguera,
S.A.Simon,
and
T.Rosenbaum
(2008).
TRPV1: on the road to pain relief.
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Curr Mol Pharmacol,
1,
255-269.
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B.Nilius,
G.Owsianik,
and
T.Voets
(2008).
Transient receptor potential channels meet phosphoinositides.
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EMBO J,
27,
2809-2816.
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B.R.Myers,
C.J.Bohlen,
and
D.Julius
(2008).
A yeast genetic screen reveals a critical role for the pore helix domain in TRP channel gating.
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Neuron,
58,
362-373.
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C.B.Phelps,
R.J.Huang,
P.V.Lishko,
R.R.Wang,
and
R.Gaudet
(2008).
Structural analyses of the ankyrin repeat domain of TRPV6 and related TRPV ion channels.
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Biochemistry,
47,
2476-2484.
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PDB code:
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E.J.Cavanaugh,
D.Simkin,
and
D.Kim
(2008).
Activation of transient receptor potential A1 channels by mustard oil, tetrahydrocannabinol and Ca2+ reveals different functional channel states.
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Neuroscience,
154,
1467-1476.
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E.J.Roh,
J.M.Keller,
Z.Olah,
M.J.Iadarola,
and
K.A.Jacobson
(2008).
Structure-activity relationships of 1,4-dihydropyridines that act as enhancers of the vanilloid receptor 1 (TRPV1).
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Bioorg Med Chem,
16,
9349-9358.
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G.Fernández-Ballester,
and
A.Ferrer-Montiel
(2008).
Molecular modeling of the full-length human TRPV1 channel in closed and desensitized states.
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J Membr Biol,
223,
161-172.
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H.Salazar,
I.Llorente,
A.Jara-Oseguera,
R.García-Villegas,
M.Munari,
S.E.Gordon,
L.D.Islas,
and
T.Rosenbaum
(2008).
A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic.
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Nat Neurosci,
11,
255-261.
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J.Snellman,
T.Kaur,
Y.Shen,
and
S.Nawy
(2008).
Regulation of ON bipolar cell activity.
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Prog Retin Eye Res,
27,
450-463.
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J.Szolcsányi
(2008).
Hot target on nociceptors: perspectives, caveats and unique features.
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Br J Pharmacol,
155,
1142-1144.
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P.Holzer
(2008).
The pharmacological challenge to tame the transient receptor potential vanilloid-1 (TRPV1) nocisensor.
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Br J Pharmacol,
155,
1145-1162.
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R.Gaudet
(2008).
A primer on ankyrin repeat function in TRP channels and beyond.
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Mol Biosyst,
4,
372-379.
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S.C.Stotz,
J.Vriens,
D.Martyn,
J.Clardy,
and
D.E.Clapham
(2008).
Citral sensing by TRANSient receptor potential channels in dorsal root ganglion neurons.
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PLoS ONE,
3,
e2082.
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T.Rohacs,
B.Thyagarajan,
and
V.Lukacs
(2008).
Phospholipase C mediated modulation of TRPV1 channels.
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Mol Neurobiol,
37,
153-163.
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V.Y.Moiseenkova-Bell,
L.A.Stanciu,
I.I.Serysheva,
B.J.Tobe,
and
T.G.Wensel
(2008).
Structure of TRPV1 channel revealed by electron cryomicroscopy.
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Proc Natl Acad Sci U S A,
105,
7451-7455.
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Y.Y.Wang,
R.B.Chang,
H.N.Waters,
D.D.McKemy,
and
E.R.Liman
(2008).
The Nociceptor Ion Channel TRPA1 Is Potentiated and Inactivated by Permeating Calcium Ions.
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J Biol Chem,
283,
32691-32703.
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C.B.Phelps,
and
R.Gaudet
(2007).
The role of the N terminus and transmembrane domain of TRPM8 in channel localization and tetramerization.
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J Biol Chem,
282,
36474-36480.
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M.Bandell,
L.J.Macpherson,
and
A.Patapoutian
(2007).
From chills to chilis: mechanisms for thermosensation and chemesthesis via thermoTRPs.
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Curr Opin Neurobiol,
17,
490-497.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
