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Vanilloid agonist-mediated activation of TRPV1 channels requires coordinated movement of the S1–S4 bundle rather than a quiescent state 被引量:2
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作者 Meng-Yang Sun Xue Zhang +14 位作者 Peng-Cheng Yu Di Liu Yang Yang Wen-Wen Cui Xiao-Na Yang Yun-Tao Lei Xing-Hua Li Wen-Hui wang Peng Cao heng-shan wang Michael X.Zhu Chang-Zhu Li Rui wang Ying-Zhe Fan Ye Yu 《Science Bulletin》 SCIE EI CSCD 2022年第10期1062-1076,M0004,共16页
Transient receptor potential vanilloid 1(TRPV1)channel plays an important role in a wide range of physiological and pathological processes,and a comprehensive understanding of TRPV1 gating will create opportunities fo... Transient receptor potential vanilloid 1(TRPV1)channel plays an important role in a wide range of physiological and pathological processes,and a comprehensive understanding of TRPV1 gating will create opportunities for therapeutic intervention.Recent incredible advances in cryo-electron microscopy(cryo-EM)have yielded high-resolution structures of all TRPV subtypes(TRPV1-6)and all of them share highly conserved six transmembrane(TM)domains(S1-S6).As revealed by the open structures of TRPV1 in the presence of a bound vanilloid agonist(capsaicin or resiniferatoxin),TM helices S1 to S4 form a bundle that remains quiescent during channel activation,highlighting differences in the gating mechanism of TRPV1 and voltage-gated ion channels.Here,however,we argue that the structural dynamics rather than quiescence of S1-S4 domains is necessary for capsaicin-mediated activation of TRPV1.Using fluorescent unnatural amino acid(flUAA)incorporation and voltage-clamp fluorometry(VCF)analysis,we directly observed allostery of the S1-S4 bundle upon capsaicin binding.Covalent occupation of VCF-identified sites,single-channel recording,cell apoptosis analysis,and exploration of the role of PSFL828,a novel non-vanilloid agonist we identified,have collectively confirmed the essential role of this coordinated S1-S4 motility in capsaicin-mediated activation of TRPV1.This study concludes that,in contrast to cryo-EM structural studies,vanilloid agonists are also required for S1-S4 movement during TRPV1 activation.Redefining the gating process of vanilloid agonists and the discovery of new non-vanilloid agonists will allow the evaluation of new strategies aimed at the development of TRPV1 modulators. 展开更多
关键词 Ligand-gated ion channels TRPV1 ALLOSTERY Voltage-clamp fluorometry Vanilloid agonist
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Photocatalyst-controlled and visible light-enabled selective oxidation of pyridinium salts
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作者 Xiang-Jun Peng Hai-Ping He +5 位作者 Qian Liu Kun She Bao-Qi Zhang heng-shan wang Hai-Tao Tang Ying-Ming Pan 《Science China Chemistry》 SCIE EI CSCD 2021年第5期753-760,共8页
This study proposes two different methods of photocatalytic-controlled and visible light-induced selective oxidation of pyridiniums with air as the terminal oxidant.The key to these transformations is to choose the ap... This study proposes two different methods of photocatalytic-controlled and visible light-induced selective oxidation of pyridiniums with air as the terminal oxidant.The key to these transformations is to choose the appropriate light source and photocatalyst.Pyridiniums are successfully converted into pyrroles through oxygen-mediated cycloaddition,proton-coupled electron transfer(PCET),pyridine ring opening,and recyclization.The other route is that pyridiniums selectively form 4-carbonyl pyridines through free radical rearrangement/aerobic oxidation under the catalysis of cobalt(Ⅱ). 展开更多
关键词 photocatalytic-controlled reaction proton-coupled electron transfer ring opening/recyclization process rearrangement/aerobic oxidation the Ladenburg rearrangement PYRIDINIUM
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