7YKR

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

Summary for 7YKR

• Entry DOI: 10.2210/pdb7ykr/pdb
• EMDB information: 33895
• Descriptor: Transient receptor potential cation channel subfamily A member 1 (1 entity in total)
• Functional Keywords: ion channel, trpa1, membrane protein
• Biological source: Drosophila melanogaster (fruit fly)
• Total number of polymer chains: 4
• Total formula weight: 541297.44

Authors

Sun, L.,Liu, X.,Yang, Z.,Wang, X. (deposition date: 2022-07-23, release date: 2023-07-26, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.2 Å)