2019
DOI: 10.1111/bph.14766
|View full text |Cite
|
Sign up to set email alerts
|

Structural mechanisms underlying activation of TRPV1 channels by pungent compounds in gingers

Abstract: Background and Purpose Like chili peppers, gingers produce pungent stimuli by a group of vanilloid compounds that activate the nociceptive transient receptor potential vanilloid 1 (TRPV1) ion channel. How these compounds interact with TRPV1 remains unclear. Experimental Approach We used computational structural modelling, functional tests (electrophysiology and calcium imaging), and mutagenesis to investigate the structural mechanisms underlying ligand–channel interactions. Key Results The potency of three pri… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

2
30
0
2

Year Published

2020
2020
2024
2024

Publication Types

Select...
4
2
1

Relationship

2
5

Authors

Journals

citations
Cited by 41 publications
(34 citation statements)
references
References 52 publications
2
30
0
2
Order By: Relevance
“…These ligands are thought to interact with both S4 and S4-S5 linker 11,18 . Cap -1 and Cap +1 in the present study and plant-derived natural ligands in previous studies 22,24 can bind in another pose without a direct interaction with S4-S5 linker, yet they produce a very similar permissive conformation of the ligand-binding pocket. Therefore, in TRPV1, the ligand recognition mechanism has evolved following the allosteric principle.…”
Section: Existence Of a Single Permissive Ligand-binding Pocket Confosupporting
confidence: 54%
See 2 more Smart Citations
“…These ligands are thought to interact with both S4 and S4-S5 linker 11,18 . Cap -1 and Cap +1 in the present study and plant-derived natural ligands in previous studies 22,24 can bind in another pose without a direct interaction with S4-S5 linker, yet they produce a very similar permissive conformation of the ligand-binding pocket. Therefore, in TRPV1, the ligand recognition mechanism has evolved following the allosteric principle.…”
Section: Existence Of a Single Permissive Ligand-binding Pocket Confosupporting
confidence: 54%
“…Movement of the S4-S5 linker away from the pore leads to subsequent S6 movement and pore opening ( Yang et al, 2015 ; Yang et al, 2018 ). A less efficacious ligand pose, used by piperine from black peppers (and zingerone from gingers), involves direct interaction with the S6 segment instead of the S4-S5 linker ( Yin et al, 2019 ; Dong et al, 2019 ). In this horizontal pose, piperine is found to bridge T551 on the S4 segment and T671 in the middle of the S6 segment, which is expected to cause S6 movement and pore opening.…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…Therefore, voltage activation cannot be carried out through the same transition promoted by capsaicin, i.e., if Scenario B is true, capsaicin cannot be stimulus X. Indeed, as capsaicin [42,43] and other pungent natural compounds [44] induce TRPV1 activation by linking S4 to the S4-S5 linker, [45] these results offered further supports for the conclusion that voltage activation does not involve S4. Furthermore, the observation of a voltage-independent, elevated P o in the presence of capsaicin also validated the conclusion that voltage cannot work through the C↔O transition to open the channel, i.e., Scenario A is invalid.…”
Section: Identifying the Voltage-dependent Transitionmentioning
confidence: 72%
“…The expansive physiological involvement of TRPV1 makes it difficult to succeed in such strategies without side-effects (Premkumar and Sikand, 2008; Szolcsanyi and Sandor, 2012). On the other hand, TRPV1 modulation by dietary components such as capsaicin (Szallasi, 2005; Yang and Zheng, 2017), piperine (Szallasi, 2005), gingerol (Yin et al, 2019) etc gave a new direction to TRPV1 oriented research. Capsaicin has been studied a lot in relation to inflammation and pain relief, and is also being investigated for its role in metabolism and related disorders like obesity (Baskaran et al, 2019; Fattori et al, 2016; Narang et al, 2017).…”
Section: Discussionmentioning
confidence: 99%