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TitleStructures of invertebrate PEZO-1 isoforms with a compact architecture and a dispensable pore-distal N-terminal blade.
Journal, issue, pagesCell Rep, Vol. 45, Issue 1, Page 116878, Year 2025
Publish dateDec 31, 2025
AuthorsBriar Bell / Angela M Jaramillo-Granada / Daniel J Orlin / Wei-Hsiang Weng / Haosheng Wen / Marcos Sotomayor / Alexander T Chesler / Matthew L Baker / Julio F Cordero-Morales / Valeria Vásquez /
PubMed AbstractPIEZO channels are mechanosensitive ion channels conserved from plants to humans, yet structures exist for only a few mammalian orthologs. We define the structural and functional diversity of ...PIEZO channels are mechanosensitive ion channels conserved from plants to humans, yet structures exist for only a few mammalian orthologs. We define the structural and functional diversity of Caenorhabditis elegans PEZO-1, a single gene with extensive alternative splicing, by determining cryo-electron microscopy structures of three representative isoforms: G (full length), K (lacking the pore-distal N-terminal blade), and L (missing most of the blade). PEZO-1G displays mechanically evoked currents yet adopts a compact, semi-flattened conformation that significantly differs from the mammalian domes. The blades exhibit a three-step slope architecture stabilized by inter-blade latching among transmembrane helical units, yielding a circular, steering-wheel-like arrangement. A wider cap enables distinct blade-cap contacts that stabilize a "toggle-down" conformation. Isoform K also exhibits mechanically evoked currents, indicating that the pore-distal N-terminal blade is dispensable for mechanoactivation. Computational membrane-deformation modeling indicates that the isoforms impose distinct curvatures on the bilayer. Our findings indicate an evolutionarily distinct architecture for PEZO-1.
External linksCell Rep / PubMed:41477764
MethodsEM (single particle)
Resolution3.1 - 3.5 Å
Structure data

74281

9zis

EMDB-74281, PDB-9zis:
C. elegans PEZO-1 Isoform G
Method: EM (single particle) / Resolution: 3.5 Å

74283

9zit

EMDB-74283, PDB-9zit:
C. elegans PEZO-1 Isoform K
Method: EM (single particle) / Resolution: 3.1 Å

Source
  • caenorhabditis elegans (invertebrata)
KeywordsMEMBRANE PROTEIN / PEZO-1 / Piezo / mechanosensation / Piezo channels / mechanosensitive ion channels / C. elegans / isoforms

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