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Structure of squirrel TRPV1 in complex with capsaicinStructure of squirrel TRPV1 in complex with capsaicin
Structural highlights
Publication Abstract from PubMedTransient receptor potential (TRP) channels are polymodal molecular sensors involved in numerous physiological processes and implicated in a variety of human diseases. Several structures of the founding member of the TRP channel family, TRPV1, are available, all of which were determined for the protein missing the N- and C-termini and the extracellular S5-P-loop. Here, we present structures of the full-length thirteen-lined ground squirrel TRPV1 solved by cryo-EM. Our structures resolve the extracellular cap domain formed by the S5-P-loops and the C-terminus that wraps around the three-stranded beta-sheet connecting elements of the TRPV1 intracellular skirt. The cap domain forms a dome above the pore's extracellular entrance, with four portals leading to the ion conductance pathway. Deletion of the cap increases the TRPV1 average conductance, reduces the open probability and affects ion selectivity. Our data show that both the termini and the cap domain are critical determinants of TRPV1 function. Extracellular cap domain is an essential component of the TRPV1 gating mechanism.,Nadezhdin KD, Neuberger A, Nikolaev YA, Murphy LA, Gracheva EO, Bagriantsev SN, Sobolevsky AI Nat Commun. 2021 Apr 12;12(1):2154. doi: 10.1038/s41467-021-22507-3. PMID:33846324[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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