An iris-like pore for protein import into peroxisomes

Rapoport, T.; He, D.; Gao, Y.

doi:10.64898/2026.10.23.761396

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bioRxiv · 10.64898/2026.10.23.761396

An iris-like pore for protein import into peroxisomes

Rapoport, T.·He, D.·Gao, Y.

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Abstract

Peroxisomes are ubiquitous, membrane-bound organelles that house essential metabolic enzymes imported from the cytosol in a folded and sometimes oligomeric state. Mobile receptors, such as PEX5, ferry cargo through a tyrosine/glycine (YG)-rich selective phase formed by PEX13 within the membrane, but how folded proteins of different sizes cross the membrane remains unknown. Here we report structures of the channel that mediates cargo import. Twelve PEX13 molecules assemble into a pore formed by a ring of tilted amphipathic helices in alternating orientations. Hydrophobic faces contact the lipid bilayer, whereas hydrophilic faces line the pore containing the YG phase. Pairs of oppositely oriented helices can slide relative to neighboring pairs and thereby alter the helix tilt angle, enabling iris-like dilation of the pore from ~52 Angstrom in the resting state to ~70 Angstrom, sufficient to accommodate the PEX5 receptor carrying small cargo. Translocation of the largest cargo requires further widening to ~100 Angstrom, a state supported by AlphaFold modeling and disulfide crosslinking. Our findings suggest that the channel provides an adaptive conduit for folded proteins of varying sizes, a mechanism distinct from other known modes of protein translocation.

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Rapoport, T., He, D., Gao, Y.. 2026-10-27. An iris-like pore for protein import into peroxisomes. https://doi.org/10.64898/2026.10.23.761396

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