Assessing Metabolite Interactions With Chloroplastic Proteins via the PISA Assay

Plants rely on metabolite regulation of proteins to control their metabolism and adapt to environmental changes, but studying these complex interaction networks remains challenging. The proteome integral solubility alteration (PISA) assay, a high-throughput chemoproteomic technique, was originally d...

Full description

Saved in:
Bibliographic Details
Main Authors: Anna Karlsson, Emil Sporre, Linnéa Strandberg, Szilvia Tóth, Elton Hudson
Format: Article
Language:English
Published: Bio-protocol LLC 2025-05-01
Series:Bio-Protocol
Online Access:https://bio-protocol.org/en/bpdetail?id=5298&type=0
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850192885597601792
author Anna Karlsson
Emil Sporre
Linnéa Strandberg
Szilvia Tóth
Elton Hudson
author_facet Anna Karlsson
Emil Sporre
Linnéa Strandberg
Szilvia Tóth
Elton Hudson
author_sort Anna Karlsson
collection DOAJ
description Plants rely on metabolite regulation of proteins to control their metabolism and adapt to environmental changes, but studying these complex interaction networks remains challenging. The proteome integral solubility alteration (PISA) assay, a high-throughput chemoproteomic technique, was originally developed for mammalian systems to investigate drug targets. PISA detects changes in protein stability upon interaction with small molecules, quantified through LC–MS. Here, we present an adapted PISA protocol for Arabidopsis thaliana chloroplasts to identify potential protein interactions with ascorbate. Chloroplasts are extracted using a linear Percoll gradient, treated with multiple ascorbate concentrations, and subjected to heat-induced protein denaturation. Soluble proteins are extracted via ultracentrifugation, and proteome-wide stability changes are quantified using multiplexed LC–MS. We provide instructions for deconvolution of LC–MS spectra and statistical analysis using freely available software. This protocol enables unbiased screening of protein regulation by small molecules in plants without requiring prior knowledge of interaction partners, chemical probe design, or genetic modifications.
format Article
id doaj-art-abf9f339d83545f29c14b167ac6f7464
institution OA Journals
issn 2331-8325
language English
publishDate 2025-05-01
publisher Bio-protocol LLC
record_format Article
series Bio-Protocol
spelling doaj-art-abf9f339d83545f29c14b167ac6f74642025-08-20T02:14:24ZengBio-protocol LLCBio-Protocol2331-83252025-05-0115910.21769/BioProtoc.5298Assessing Metabolite Interactions With Chloroplastic Proteins via the PISA AssayAnna Karlsson0Emil Sporre1Linnéa Strandberg2Szilvia Tóth3Elton Hudson4School of Engineering Science in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, SwedenSchool of Engineering Science in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, SwedenInstitute for Integrative Biology of the Cell, Université Paris-Saclay, Paris, FranceSchool of Engineering Science in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, SwedenSchool of Engineering Science in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, SwedenPlants rely on metabolite regulation of proteins to control their metabolism and adapt to environmental changes, but studying these complex interaction networks remains challenging. The proteome integral solubility alteration (PISA) assay, a high-throughput chemoproteomic technique, was originally developed for mammalian systems to investigate drug targets. PISA detects changes in protein stability upon interaction with small molecules, quantified through LC–MS. Here, we present an adapted PISA protocol for Arabidopsis thaliana chloroplasts to identify potential protein interactions with ascorbate. Chloroplasts are extracted using a linear Percoll gradient, treated with multiple ascorbate concentrations, and subjected to heat-induced protein denaturation. Soluble proteins are extracted via ultracentrifugation, and proteome-wide stability changes are quantified using multiplexed LC–MS. We provide instructions for deconvolution of LC–MS spectra and statistical analysis using freely available software. This protocol enables unbiased screening of protein regulation by small molecules in plants without requiring prior knowledge of interaction partners, chemical probe design, or genetic modifications.https://bio-protocol.org/en/bpdetail?id=5298&type=0
spellingShingle Anna Karlsson
Emil Sporre
Linnéa Strandberg
Szilvia Tóth
Elton Hudson
Assessing Metabolite Interactions With Chloroplastic Proteins via the PISA Assay
Bio-Protocol
title Assessing Metabolite Interactions With Chloroplastic Proteins via the PISA Assay
title_full Assessing Metabolite Interactions With Chloroplastic Proteins via the PISA Assay
title_fullStr Assessing Metabolite Interactions With Chloroplastic Proteins via the PISA Assay
title_full_unstemmed Assessing Metabolite Interactions With Chloroplastic Proteins via the PISA Assay
title_short Assessing Metabolite Interactions With Chloroplastic Proteins via the PISA Assay
title_sort assessing metabolite interactions with chloroplastic proteins via the pisa assay
url https://bio-protocol.org/en/bpdetail?id=5298&type=0
work_keys_str_mv AT annakarlsson assessingmetaboliteinteractionswithchloroplasticproteinsviathepisaassay
AT emilsporre assessingmetaboliteinteractionswithchloroplasticproteinsviathepisaassay
AT linneastrandberg assessingmetaboliteinteractionswithchloroplasticproteinsviathepisaassay
AT szilviatoth assessingmetaboliteinteractionswithchloroplasticproteinsviathepisaassay
AT eltonhudson assessingmetaboliteinteractionswithchloroplasticproteinsviathepisaassay