What question did this study set out to answer?

The aim is to identify peptides that interfere with the interaction between PP2Ac and LRRK2, a protein linked to Parkinson's disease.

April 19, 2026Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics0 citationsOpen Access

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Identification of peptides interfering with the PP2Ac And LRRK2 interaction

ARAngelita RebolloCentre National de la Recherche Scientifique SMSamuel MurailCentre National de la Recherche Scientifique PTPierre TufféryCentre National de la Recherche Scientifique

Key Points

The aim is to identify peptides that interfere with the interaction between PP2Ac and LRRK2, a protein linked to Parkinson's disease.
Employed PEP-scan approach to identify binding sites on PP2Ac and LRRK2.
Isolated peptide fragments and assessed their compatibility with LRRK2/PP2Ac interaction.
Conducted in vitro competition experiments to evaluate the effectiveness of identified peptides.
Identified specific peptides (P3 and M1) that effectively compete for PP2A/LRRK2 interaction.
Peptides are predicted to be solvent-accessible and likely adopt helical conformations.
Peptide M2 did not show compatibility with the interaction, while others may serve as tools for further study.

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.

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Cite This Study

Rebollo et al. (Wed,) studied this question.

synapsesocial.com/papers/69e4702d010ef96374d8d622 https://doi.org/https://doi.org/10.1016/j.bbapap.2026.141145

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