Modulation of TRP Ion Channels by Venomous Toxins

Siemens, Jan; Hanack, Christina

doi:10.1007/978-3-319-05161-1_17

Cited by 8 publications

(6 citation statements)

References 126 publications

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“…The models quality was evaluated with the MOE 15.1001 software and PROCHECK [81] server. Since the receptor structures obtained by cryoelectron microscopy (3J5Q, 3J5R, 5IRZ, 5IRX, 5IS0) omitted more than 110 N-terminal and 71 C-terminal residues that form regulatory receptor domain and provide engagement TRPV1 interaction with inhibitory proteins (calmodulin) [82] and other intracellular partners, our TRPV1 model is adequate for transmembrane, as well as extracellular domains, including extracellular loops 2 and 3.…”

Section: Methodsmentioning

confidence: 99%

Kunitz-Type Peptide HCRG21 from the Sea Anemone Heteractis crispa Is a Full Antagonist of the TRPV1 Receptor

et al. 2016

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Sea anemone venoms comprise multifarious peptides modulating biological targets such as ion channels or receptors. The sequence of a new Kunitz-type peptide, HCRG21, belonging to the Heteractis crispa RG (HCRG) peptide subfamily was deduced on the basis of the gene sequence obtained from the Heteractis crispa cDNA. HCRG21 shares high structural homology with Kunitz-type peptides APHC1–APHC3 from H. crispa, and clusters with the peptides from so named “analgesic cluster” of the HCGS peptide subfamily but forms a separate branch on the NJ-phylogenetic tree. Three unique point substitutions at the N-terminus of the molecule, Arg1, Gly2, and Ser5, distinguish HCRG21 from other peptides of this cluster. The trypsin inhibitory activity of recombinant HCRG21 (rHCRG21) was comparable with the activity of peptides from the same cluster. Inhibition constants for trypsin and α-chymotrypsin were 1.0 × 10−7 and 7.0 × 10−7 M, respectively. Electrophysiological experiments revealed that rHCRG21 inhibits 95% of the capsaicin-induced current through transient receptor potential family member vanilloid 1 (TRPV1) and has a half-maximal inhibitory concentration of 6.9 ± 0.4 μM. Moreover, rHCRG21 is the first full peptide TRPV1 inhibitor, although displaying lower affinity for its receptor in comparison with other known ligands. Macromolecular docking and full atom Molecular Dynamics (MD) simulations of the rHCRG21–TRPV1 complex allow hypothesizing the existence of two feasible, intra- and extracellular, molecular mechanisms of blocking. These data provide valuable insights in the structural and functional relationships and pharmacological potential of bifunctional Kunitz-type peptides.

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Section: Methodsmentioning

confidence: 99%

Kunitz-Type Peptide HCRG21 from the Sea Anemone Heteractis crispa Is a Full Antagonist of the TRPV1 Receptor

et al. 2016

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“…Gradual appreciation of TRP channels can be traced through review articles that act as milestones in understanding their physiological function 6, 9-19, regulation by associated proteins 20-22, evolution 23, intracellular trafficking 24, 25, pre-mRNA splicing 26, and interactions with immune cells 27. Monographs of the TRP field have also appeared 28-31. The last specific review of the role of TRPV6 in cancer was published in 2012 32 with reference to cancer in reviews of larger scope 23, 33, 34.…”

Section: Introductionmentioning

confidence: 99%

TRPV6 as A Target for Cancer Therapy

Stewart¹

2020

J. Cancer

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Two decades ago a class of ion channels, hitherto unsuspected, was discovered. In mammals these Transient Receptor Potential channels (TRPs) have not only expanded in number (to 26 functional channels) but also expanded the view of our interface with the physical and chemical environment. Some are heat and cold sensors while others monitor endogenous and/or exogenous chemical signals. Some TRP channels monitor osmotic potential, and others measure cell movement, stretching, and fluid flow. Many TRP channels are major players in nociception and integration of pain signals. One member of the vanilloid sub-family of channels is TRPV6. This channel is highly selective for divalent cations, particularly calcium, and plays a part in general whole-body calcium homeostasis, capturing calcium in the gut from the diet. TRPV6 can be greatly elevated in a number of cancers deriving from epithelia and considerable study has been made of its role in the cancer phenotype where calcium control is dysfunctional. This review compiles and updates recent published work on TRPV6 as a promising drug target in a number of cancers including those afflicting breast, ovarian, prostate and pancreatic tissues.

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“…GSK2798745 is a TRPV4 antagonist that was developed to treat pulmonary edema associated with heart failure, while another substance inhibiting TRPC4 and TRPC5 targets depression and anxiety disorder [ 127 , 128 ]. In addition, TRP channels are also affected by various venomous toxins [ 152 , 153 , 154 , 155 , 156 , 157 ] which have been suggested to be used for the treatment of COVID-19, most notably resiniferatoxin (RTX) [ 158 ]. It will be interesting to see which of these candidates have the potential to be applied for COVID-19 in a widespread clinical setting.…”

Section: Emerging Treatment Strategiesmentioning

confidence: 99%

Calcium Signals during SARS-CoV-2 Infection: Assessing the Potential of Emerging Therapies

Berlansky

Sallinger

Grabmayr

et al. 2022

Cells

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). This respiratory illness was declared a pandemic by the world health organization (WHO) in March 2020, just a few weeks after being described for the first time. Since then, global research effort has considerably increased humanity’s knowledge about both viruses and disease. It has also spawned several vaccines that have proven to be key tools in attenuating the spread of the pandemic and severity of COVID-19. However, with vaccine-related skepticism being on the rise, as well as breakthrough infections in the vaccinated population and the threat of a complete immune escape variant, alternative strategies in the fight against SARS-CoV-2 are urgently required. Calcium signals have long been known to play an essential role in infection with diverse viruses and thus constitute a promising avenue for further research on therapeutic strategies. In this review, we introduce the pivotal role of calcium signaling in viral infection cascades. Based on this, we discuss prospective calcium-related treatment targets and strategies for the cure of COVID-19 that exploit viral dependence on calcium signals.

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Modulation of TRP Ion Channels by Venomous Toxins

Cited by 8 publications

References 126 publications

Kunitz-Type Peptide HCRG21 from the Sea Anemone Heteractis crispa Is a Full Antagonist of the TRPV1 Receptor

Kunitz-Type Peptide HCRG21 from the Sea Anemone Heteractis crispa Is a Full Antagonist of the TRPV1 Receptor

TRPV6 as A Target for Cancer Therapy

Calcium Signals during SARS-CoV-2 Infection: Assessing the Potential of Emerging Therapies

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