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Signal sequences are short amino acid sequences that guide newly synthesized proteins to their proper location within the cell. Classical signal sequences are fifteen to sixty amino acids long and present at the N-terminus of a polypeptide chain. Each signal sequence has a conserved segment of basic residues towards their N terminus, a hydrophobic core, and a C-terminus rich in polar residues. The C-terminus also contains a signal cleavage site and features a -3 -1 sequence motif. The -3-1...
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Updated: Apr 8, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
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pLM-Repeat: Exploiting the sequence representations of protein language models for sensitive repeat detection.

Kaiyu Qiu1, Andrei N Lupas1, Stanislaw Dunin-Horkawicz1,2

  • 1Department of Protein Evolution, Max Planck Institute for Biology Tübingen, Tübingen, Germany.

Protein Science : a Publication of the Protein Society
|April 7, 2026
PubMed
Summary
This summary is machine-generated.

We developed pLM-Repeat, a new tool for detecting protein repeats. It is faster and more sensitive than existing methods, enabling the discovery of novel repeat proteins.

Keywords:
AlphaFold databasebioinformatic toolprotein language modelrepeat proteinsequence analysis

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Area of Science:

  • Molecular Biology
  • Bioinformatics
  • Computational Biology

Background:

  • Duplication is crucial for molecular evolution and protein evolution.
  • Detecting ancient duplications is challenging due to sequence divergence.
  • Current methods like HHrepID are sensitive but slow, limiting large-scale analysis.

Purpose of the Study:

  • To introduce pLM-Repeat, a novel pipeline for identifying protein repeat patterns.
  • To leverage protein language models (pLMs) for faster and more sensitive repeat detection.
  • To discover novel repeat proteins using pLM-Repeat and the AlphaFold Protein Structure Database.

Main Methods:

  • Utilized sequence embeddings from protein language models (pLMs) via pLM-BLAST.
  • Developed the pLM-Repeat pipeline to analyze repeat patterns in sequence representations.
  • Employed a pre-filtering model trained on repeat protein representations for novel protein discovery.

Main Results:

  • pLM-Repeat demonstrates comparable sensitivity to HHrepID for repeat detection.
  • pLM-Repeat identifies a greater number of repeat units compared to existing methods.
  • The tool significantly reduces runtime, enabling efficient large-scale scans.
  • Novel repeat proteins were identified in the AlphaFold Protein Structure Database.

Conclusions:

  • pLM-Repeat offers a sensitive and rapid approach for detecting protein repeats.
  • The pipeline enhances the study of molecular evolution and protein structure.
  • pLM-Repeat facilitates the discovery of previously unknown repeat proteins.