Structures of Invertebrate Pezo-1 Isoforms With a Compact Architecture and a Dispensable Pore-Distal N-terminal Blade

Authors

Briar 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

Language

English

Publication Date

1-27-2026

Journal

Cell Reports

DOI

10.1016/j.celrep.2025.116878

PMID

41477764

Abstract

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.

Keywords

Animals, Protein Isoforms, Caenorhabditis elegans Proteins, Caenorhabditis elegans, Cryoelectron Microscopy, Ion Channels, Amino Acid Sequence, Models, Molecular, Humans, C. elegans, CP: neuroscience, PEZO-1, PIEZO1, PIEZO2, coarse-grained molecular dynamics, cryo-EM, electrophysiology, isoforms, mechanosensitive ion channels, membrane deformation, splice variants

Published Open-Access

yes

Recommended Citation

Bell, Briar; Jaramillo-Granada, Angela M; Orlin, Daniel J; et al., "Structures of Invertebrate Pezo-1 Isoforms With a Compact Architecture and a Dispensable Pore-Distal N-terminal Blade" (2026). Faculty, Staff and Student Publications. 5491.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5491