Lipid-dependent sequential allosteric activation of heat-sensing TRPV1 channels by anchor-stereoselective “hot” vanilloid compounds and analogs

Biochemistry and Biophysics Reports

Guangyu Wang¹ 

[1] Department of Physiology and Membrane Biology, University of California School of Medicine, Davis, CA, USA;

关键词: Sequential cooperativity;    Active site stereoselectivity;    Dominant steady-state ligand binding;    Recessive transient ligand binding;    Lipid-ligand interaction;    Hydrogen bonding network;   

DOI  :  

来源: DOAJ

【 摘 要 】

Both a silent resident phosphatidylinositol lipid and a “hot” vanilloid agonist capsaicin or resiniferatoxin have been shown to share the same inter-subunit binding pocket between a voltage sensor like domain and a pore domain in TRPV1. However, how the vanilloid competes off the resident lipid for allosteric TRPV1 activation is unknown. Here, the in silico research suggested that anchor-stereoselective sequential cooperativity between an initial recessive transient silent weak ligand binding site and a subsequent dominant steady-state strong ligand binding site in the vanilloid pocket may facilitate the lipid release for allosteric activation of TRPV1 by vanilloids or analogs upon non-covalent interactions. Thus, the resident lipid may play a critical role in allosteric activation of TRPV1 by vanilloid compounds and analogs.

【 授权许可】

Unknown