What they found
Cryo-EM structure of PCDH15 — the lower tip link protein that connects stereocilia and gates mechanotransduction channels. PCDH15 forms parallel cis-dimers arranged as a right-handed double helix. This specific oligomeric architecture is required for tip link function: mutations that disrupt dimerization impair mechanotransduction even when the protein is expressed and present. Architecture = function, not just presence.
How this applies to mini-STRC
Stereocilin and PCDH15 are both extracellular proteins that form load-bearing connections between stereocilia structures. The PCDH15 finding generalizes: in the hair bundle, extracellular connector proteins don’t just need to be present — they need to self-assemble into precise supramolecular structures. Mini-STRC must therefore preserve not only folding stability but oligomerization capacity. The truncation at residues 700–1775 may disrupt self-assembly domains that exist outside this window. Computationally: predict STRC oligomeric state with AlphaFold-Multimer, identify self-assembly interfaces, verify they fall within the mini-STRC window.
Key numbers
- PCDH15 architecture: right-handed double helix parallel cis-dimer
- Dimerization domain mutations: impair mechanotransduction even with normal expression levels
- Technique: cryo-EM
Links
- bioRxiv: https://biorxiv.org/content/10.64898/2026.03.02.709101
- DOI: https://doi.org/10.64898/2026.03.02.709101
Connections
- STRC Mini-STRC Single-Vector Hypothesis — generalizes oligomerization constraint; AF3-Multimer STRC homodimer becomes required step