7YKR

Structure of TRPA1 in Drosophila melanogaster in a state with 17 ankyrin repeats determined

7YKR の概要

• エントリーDOI: 10.2210/pdb7ykr/pdb
• EMDBエントリー: 33895
• 分子名称: Transient receptor potential cation channel subfamily A member 1 (1 entity in total)
• 機能のキーワード: ion channel, trpa1, membrane protein
• 由来する生物種: Drosophila melanogaster (fruit fly)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 541297.44

構造登録者

Sun, L.,Liu, X.,Yang, Z.,Wang, X. (登録日: 2022-07-23, 公開日: 2023-07-26, 最終更新日: 2024-11-13)

主引用文献

Wang, X.,Li, Y.,Wei, H.,Yang, Z.,Luo, R.,Gao, Y.,Zhang, W.,Liu, X.,Sun, L.
Molecular architecture and gating mechanisms of the Drosophila TRPA1 channel.
Cell Discov, 9:36-36, 2023

PubMed Abstract: The transient receptor potential channel subfamily A member 1 (TRPA1) ion channel is an evolutionary conserved polymodal sensor responding to noxious temperature or chemical stimuli. Notably, the thermosensitivity of TRPA1 varies among different species or even different isoforms in the same species. However, the underlying molecular basis of its thermo-gating remains largely unknown. Here, we determine the structures of a heat-sensitive isoform of TRPA1 in Drosophila melanogaster in two distinct conformations with cryo-samples prepared at 8 °C. Large conformational changes are observed in the ankyrin repeat domain (ARD) and the coiled-coil domain between the two states. Remarkably, all 17 ankyrin repeats are mapped in the newly resolved conformation, forming a propeller-like architecture. Two intersubunit interfaces are identified in the amino (N)-terminal domain, and play vital roles during both heat and chemical activation as shown by electrophysiological analysis. With cryo-samples prepared at 35 °C, only one conformation is resolved, suggesting possible state transitions during heat responses. These findings provide a basis for further understanding how the ARD regulates channel functions, and insights into the gating mechanism of TRPA1.

PubMed: 37015924
DOI: 10.1038/s41421-023-00527-1

実験手法

ELECTRON MICROSCOPY (3.2 Å)