STRC Research

STRC Signal Peptide Validation

2 min read

STRC Signal Peptide Validation

The Problem

All mini-STRC constructs remove the native signal peptide (residues 1-26). Without SP, protein stays cytoplasmic: no ER entry, no GPI-anchor, no glycosylation, no surface display. Functionally dead.

Native STRC SP: MALSLWPLLLLLLLLLLLSFAVTLAP (26 aa, unusually long, 17 consecutive leucines)

Solution: IgK Signal Peptide

IgK (immunoglobulin kappa chain leader): METDTLLLWVLLLWVPGSTGD (21 aa, 63 bp)

Most widely used exogenous SP in gene therapy. Short, efficiently cleaved, well-characterized across cell types. Canonical Sec/SPI n-h-c pattern:

  • n-region: M-E (charged)
  • h-region: TLLLWVLLLWV (hydrophobic core)
  • c-region: PGSTGD (polar, clean Ala-x-Ala cleavage motif)

SignalP 6.0 Validation (2026-03-19)

Tool: SignalP 6.0 (DTU Health Tech). Gold-standard neural network for SP prediction.

Job ID: 69BB889D0023BDA83618DAE9

ConstructSP probabilityCleavage siteCleavage PrStatus
Full STRC (native, 1775 aa)93.4%pos 24-250.689SP detected
IgK-SP + shorter mini-STRC99.97%pos 20-210.978SP detected
Shorter mini-STRC (no SP, control)0.00%——No SP

Key finding: IgK SP scores higher than native STRC SP (99.97% vs 93.4%, cleavage 0.978 vs 0.689). STRC’s native SP has an atypical hydrophobic core (17 leucines), which makes it harder for SignalP to classify confidently.

Files

  • SignalP plot (IgK construct): ~/Sites/site-strc-egor-lol/public/images/signalp-igk-mini-strc.png
  • SignalP plot (full STRC): ~/Sites/site-strc-egor-lol/public/images/signalp-full-strc.png
  • Raw prediction: https://services.healthtech.dtu.dk/services/SignalP-6.0/tmp/69BB889D0023BDA83618DAE9/prediction_results.txt
  • FASTA input: /tmp/signalp_input.fasta

Published

Section 9 of Mini-STRC page on strc.egor.lol (deploy 039d3401).

Connections

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