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Updated: May 21, 2026

Genome-wide Protein-protein Interaction Screening by Protein-fragment Complementation Assay (PCA) in Living Cells
Published on: March 3, 2015
How many protein-protein interactions types exist in nature?
Leonardo Garma1, Srayanta Mukherjee, Pralay Mitra
1Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America.
The universe of protein interactions is finite, with an estimated 4,000 possible quaternary folds. Current data covers only 42% of these protein complex structures, requiring extensive future research.
Area of Science:
- Structural Biology
- Bioinformatics
- Computational Biology
Background:
- Protein quaternary structure describes the arrangement of multiple protein subunits in a complex.
- Understanding the diversity of protein-protein interactions is crucial for deciphering biological functions.
Purpose of the Study:
- To determine if the number of protein-protein interactions is limited.
- To estimate the total number of distinct quaternary folds in nature.
Main Methods:
- All-to-all sequence and structure comparisons of protein complexes from the Protein Data Bank (PDB).
- Development of a statistical model to relate quaternary families and folds.
- Estimation of the total number of possible protein-protein interactions.
Main Results:
- Categorized PDB protein complexes into 3,629 families and 1,761 folds.
- Estimated the total number of possible protein-protein interactions to be approximately 4,000.
- Concluded that current repositories contain only 42% of known quaternary folds.
Conclusions:
- The diversity of protein quaternary structures is finite and estimated at around 4,000 folds.
- Significant experimental effort is needed to achieve complete coverage of known protein complex structures.
- Findings impact protein complex modeling and the structural genomics of protein interactions.
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