Conserved Allosteric Pathways for Activation of TRPV3 Revealed through Engineering Vanilloid-Sensitivity
نویسندگان
چکیده
منابع مشابه
Differential regulation of TRPV1, TRPV3, and TRPV4 sensitivity through a conserved binding site on the ankyrin repeat domain.
Transient receptor potential vanilloid (TRPV) channels, which include the thermosensitive TRPV1-V4, have large cytoplasmic regions flanking the transmembrane domain, including an N-terminal ankyrin repeat domain. We show that a multiligand binding site for ATP and calmodulin previously identified in the TRPV1 ankyrin repeat domain is conserved in TRPV3 and TRPV4, but not TRPV2. Accordingly, TRP...
متن کاملSupplemental Information Differential regulation of TRPV1, TRPV3 and TRPV4 sensitivity through a conserved binding site on the ankyrin repeat domain
The alignment was colored with identical residues in black and similar residues in grey. Amino acids that contact ATP in the crystal structure of the TRPV1-ARD (PDB ID 2PNN) are indicated by purple arrows above the sequences. Colored bars above the sequence indicate the individual ankyrin repeats. An insertion and two deletions in the TRPV3-ARD compared to TRPV1 and TRPV4 are indicated by light...
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The TRPV1 channel is a detector of noxious stimuli, including heat, acidosis, vanilloid compounds and lipids. The gating mechanisms of the related TRPV2 channel are poorly understood because selective high affinity ligands are not available, and the threshold for heat activation is extremely high (>50°C). Cryo-EM structures of TRPV1 and TRPV2 reveal that they adopt similar structures, and ident...
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Thermal transient receptor potential (TRP) channels, a group of ion channels from the transient receptor potential family, play important functions in pain and thermal sensation. These channels are directly activated by temperature and possess strong temperature dependence. Furthermore, their temperature sensitivity can be highly dynamic and use-dependent. For example, the vanilloid receptor tr...
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The detection and characterization of binding pockets and allosteric communication in proteins is crucial for studying biological regulation and performing drug design. Nowadays, ever-longer molecular dynamics (MD) simulations are routinely used to investigate the spatiotemporal evolution of proteins. Yet, there is no computational tool that can automatically detect all the pockets and potentia...
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ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2019
ISSN: 0006-3495
DOI: 10.1016/j.bpj.2018.11.2881