7ras | pdb_00007ras

Structure of TRPV3 in complex with osthole

spinqualitylabelsall models 7ras, resolution 3.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ras is a 4 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: A0O Gene: Trpv3 (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TRPV3_MOUSE] Putative receptor-activated non-selective calcium permeant cation channel. It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius. Activation exhibits an outward rectification. May associate with TRPV1 and may modulate its activity. Is a negative regulator of hair growth and cycling: TRPV3-coupled signaling suppresses keratinocyte proliferation in hair follicles and induces apoptosis and premature hair follicle regression (catagen) (By similarity). Publication Abstract from PubMed TRPV3, a representative of the vanilloid subfamily of TRP channels, is predominantly expressed in skin keratinocytes and has been implicated in cutaneous sensation and associated with numerous skin pathologies and cancers. TRPV3 is inhibited by the natural coumarin derivative osthole, an active ingredient of Cnidium monnieri, which has been used in traditional Chinese medicine for the treatment of a variety of human diseases. However, the structural basis of channel inhibition by osthole has remained elusive. Here we present cryo-EM structures of TRPV3 in complex with osthole, revealing two types of osthole binding sites in the transmembrane region of TRPV3 that coincide with the binding sites of agonist 2-APB. Osthole binding converts the channel pore into a previously unidentified conformation with a widely open selectivity filter and closed intracellular gate. Our structures provide insight into competitive inhibition of TRPV3 by osthole and can serve as a template for the design of osthole chemistry-inspired drugs targeting TRPV3-associated diseases. Structural mechanism of TRPV3 channel inhibition by the plant-derived coumarin osthole.,Neuberger A, Nadezhdin KD, Zakharian E, Sobolevsky AI EMBO Rep. 2021 Sep 2:e53233. doi: 10.15252/embr.202153233. PMID:34472684 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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