Identification of peptides interfering with the PP2Ac And LRRK2 interaction

Using the PEP-scan approach, we have identified the binding site of PP2Ac to LRRK2, a protein associated with Parkinson's disease. We also have identified the binding site of LRRK2 to PP2Ac, referred to as mirror peptide. All isolated fragments are predicted to be solvent-accessible and are compatible with contributing to LRRK2/PP2Ac interaction except for peptide M2. The In vitro competition experiment demonstrated that peptide P3 and M1 effectively compete PP2A/LRRK2 interaction. Both appear to have propensity to adopt helical conformation. These newly generated peptides can be tools to investigate the role of PP2A/LRRK2 interaction under both physiological and pathological conditions.

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Journal
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Published
2026-04-15
DOI
https://doi.org/10.1016/j.bbapap.2026.141145
Primary Topic
Protein Kinase Regulation and GTPase Signaling
Type
article
Field-Weighted Citation Impact
0.00

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article

Identification of peptides interfering with the PP2Ac And LRRK2 interaction

Pierre Tufféry, Samuel Murail, Angelita Rebollo
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Protein Kinase Regulation and GTPase Signaling
article

Identification of peptides interfering with the PP2Ac And LRRK2 interaction

Pierre Tufféry, Samuel Murail, Angelita Rebollo
article en

Abstract

Using the PEP-scan approach, we have identified the binding site of PP2Ac to LRRK2, a protein associated with Parkinson's disease. We also have identified the binding site of LRRK2 to PP2Ac, referred to as mirror peptide. All isolated fragments are predicted to be solvent-accessible and are compatible with contributing to LRRK2/PP2Ac interaction except for peptide M2. The In vitro competition experiment demonstrated that peptide P3 and M1 effectively compete PP2A/LRRK2 interaction. Both appear to have propensity to adopt helical conformation. These newly generated peptides can be tools to investigate the role of PP2A/LRRK2 interaction under both physiological and pathological conditions.

Biochimica et Biophysica Acta (BBA) - Proteins and ProteomicsVol. 1874(4)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Paris Cité (FR), Unit of Functional and Adaptive Biology (FR), Unité de Technologies Chimiques et Biologiques pour la Santé (FR)
Institut National de la Santé et de la Recherche Médicale
Openalex Percentile: Top 13%
Protein Kinase Regulation and GTPase Signaling
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