Structure-resolved fold annotation of the medicinal-leech salivary-EV cargo: a Ly-6/uPAR three-finger scaffold and a structurally dark fraction

Predicted structures for Hirudinaria manillensis salivary EV cargo identify the leech Protein-sleepless homolog g21166 as a Ly-6/uPAR three-finger fold, with TM 0.58 versus CD59.

• Why it matters: Sequence-based annotation leaves much of the medicinal-leech salivary EV secretome without interpretable fold assignments, limiting structure-informed prioritization for pharmacologically relevant cargo.
• What they did: Using an offline pipeline (ESMFold, TM-align, Foldseek against AFDB-SwissProt and PDB100, plus UniRef90 and protein-to-genome alignment), the 17 Astral-DIA candidates were screened under prespecified match criteria.
• The result: Two other candidates (g436, g20791) failed to meet alnTM ≥ 0.5 and E ≤ 0.05 in either database, while the structure-informed shortlist supports experimental follow-up.

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