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TitleMolecular architecture and gating mechanisms of the Drosophila TRPA1 channel.
Journal, issue, pagesCell Discov, Vol. 9, Issue 1, Page 36, Year 2023
Publish dateApr 4, 2023
AuthorsXiaofei Wang / Yawen Li / Hong Wei / Zhisen Yang / Rui Luo / Yongxiang Gao / Wei Zhang / Xin Liu / Linfeng Sun /
PubMed AbstractThe 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 ...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.
External linksCell Discov / PubMed:37015924 / PubMed Central
MethodsEM (single particle)
Resolution3.0 - 3.2 Å
Structure data

33895

7ykr

EMDB-33895, PDB-7ykr:
Structure of TRPA1 in Drosophila melanogaster in a state with 17 ankyrin repeats determined
Method: EM (single particle) / Resolution: 3.2 Å

33896

7yks

EMDB-33896, PDB-7yks:
Structure of TRPA1 in Drosophila melanogaster in a state with 5 ankyrin repeats determined
Method: EM (single particle) / Resolution: 3.0 Å

Source
  • drosophila melanogaster (fruit fly)
KeywordsMEMBRANE PROTEIN / ion channel / TRPA1

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