Home Analytical Chem A Protocol for the Identification of Protein-protein Interactions Based on 15N Metabolic Labeling, Immunoprecipitation, Quantitative Mass Spectrometry and Affinity Modulation
Analytical Chem JoVE (Open Access) Citable · DOI

A Protocol for the Identification of Protein-protein Interactions Based on 15N Metabolic Labeling, Immunoprecipitation, Quantitative Mass Spectrometry and Affinity Modulation

DOI: 10.3791/4083-v
What you'll learn
  • Perform 15N metabolic labeling of cells
  • Immunoprecipitate protein complexes under ATP modulation
  • Prepare samples for quantitative mass spectrometry
  • Distinguish true from false protein interactions
Protocol

Biopharma Insights We present a variation of the QUICK (QUantitative Immunoprecipitation Combined with Knockdown) approach that was introduced previously to distinguish between true and false protein-protein interactions. Our approach is based on 15N metabolic labeling, the modulation of affinities of protein-protein interactions by the presence/absence of ATP, immunoprecipitation, and quantitative mass spectrometry.

Difficulty
advanced
Total time
~3-4 days
Model organism
Chlamydomonas reinhardtii
Biosafety
BSL-1

Steps

1
Lyse cells and crosslink proteins

Perform cell lysis and chemical crosslinking to stabilize protein-protein interactions for subsequent analysis.

▶ 02:30
2
Immunoprecipitate target protein complexes

Use antibodies to pull down the protein of interest along with its interaction partners, with or without ATP to modulate affinities.

▶ 05:22
3
Prepare samples for nano-LC-MS/MS

Process immunoprecipitated samples, including digestion and cleanup, for subsequent quantitative mass spectrometry analysis.

▶ 07:06
4
Analyze results for HSP70B interactors

Review representative results showing identification of HSP70B interactions with its nucleotide exchange factor CGE1.

▶ 10:50
💬 Comments coming soon