Brief Introduction of Protein‑Protein Interaction (PPI)
- Advantages: high throughput; suitable for identifying novel interactions.
- Limitations: relatively high rate of false positives; constrained by protein localization in cells.
- Advantages: well suited for validating known interactions; performed under physiological conditions.
- Limitations: strongly dependent on antibody quality; often insufficient for detecting weak interactions.
- Advantages: enables proteome-scale mapping of interaction networks.
- Limitations: requires high-quality protein enrichment and highly accurate mass spectrometry platforms.
- Advantages: permits in situ identification of interacting proteins within living cells, enabling detection of transient or weak interactions.
- Limitations: relatively high background signals; experimental conditions require optimization.
- STRING: integrates both predicted and experimentally derived data
- BioGRID: manually curated from published literature
- IntAct, DIP, MINT and other international databases
Within the highly complex microscopic environment of the cell, proteins rarely function in isolation. From signal transduction to metabolic regulation, and from cytoskeletal organization to transcriptional control, nearly all biological activities depend on finely coordinated interactions among proteins. These interactions, collectively termed protein–protein interactions (PPI), involve the formation of stable or transient complexes between two or more protein molecules through noncovalent forces such as hydrogen bonding, hydrophobic interactions, and electrostatic interactions. Investigating PPIs not only helps elucidate protein functions and pathway mechanisms but also plays an essential role in studies of disease mechanisms, identification of novel drug targets, and systems-level biological modeling.
Three Basic Types of PPI
1. Stable Complexes
(1) Examples: ribosomes, proteasomes, transcription factor complexes
(2) Function: structural maintenance and enzymatic catalysis
2. Transient Interactions
(1) Examples: tyrosine kinases and their substrates, G proteins and their effector molecules
(2) Function: signal transduction and stimulus response
3. Regulatory Interactions
(1) Examples: the association between protein inhibitors and target enzymes
(2) Function: negative feedback regulation and modulation of protein activity, including inhibition or activation
Overview of Methods for PPI
Research on protein–protein interactions is broadly divided into experimental approaches and computational strategies.
1. Experimental Methods (Wet-lab)
(1) Yeast Two-Hybrid (Y2H)
(2) Co-immunoprecipitation (Co-IP)
(3) Affinity Purification–Mass Spectrometry (AP-MS / LC-MS/MS)
(4) Biotin-based Proximity Labeling (BioID, TurboID)
2. Computational Prediction (In silico)
(1) Sequence- or Structure-based Prediction
Examples include structure docking, homology modeling, and machine-learning models. These approaches are useful for identifying potential PPI interfaces but still require experimental validation.
(2) Integration of PPI Databases
Examples:
Key Application Scenarios of PPI
1. Elucidation of Disease Mechanisms
Identification of disease-associated interaction modules, such as cancer signaling pathways or viral infection routes, enables researchers to determine the network positions and functional roles of pathogenic proteins.
2. Drug Target Discovery
Development of PPI modulators, including PPI inhibitors and molecular-glue–based therapeutics, leverages druggable interaction interfaces to enhance the efficiency of lead compound screening.
3. Synthetic Biology and Systems Modeling
Construction of artificial interaction networks allows precise control of specific functional pathways, facilitating the development of dynamic models of cellular signaling networks.
Protein–protein interactions form not only the basis of individual biological processes but also the structural logic underlying the operation of the entire living system. Whether the goal is to uncover disease mechanisms or develop innovative drug targets, a comprehensive understanding of PPIs is indispensable. MtoZ Biolabs is dedicated to providing researchers and industrial R&D teams with reliable technological platforms and professional support, enabling deeper systems-level analysis and functional discovery beyond protein interaction studies.
MtoZ Biolabs, an integrated chromatography and mass spectrometry (MS) services provider.
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