Chaperone-substrate interactions monitored via a robust TEM-1 β-lactamase fragment complementation assay
Related Experiment Video
Updated: Mar 2, 2026

A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing
Published on: July 3, 2016
Ling Bai1, Wei He1, Tianpeng Li1
1State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB), East China University of Science and Technology, 130 Meilong Rd, Shanghai, 200237, China.
Objective:
To investigate the application of the TEM-1 β-lactamase protein fragment complementation assay (PCA) in detecting weak and unstable protein-protein interactions as typically observed during chaperone-assisted protein folding in the periplasm of Escherichia coli.
Results:
The TEM-1 β-lactamase PCA system effectively captured the interactions of three pairs of chaperones and substrates. Moreover, the strength of the interactions can be quantitatively analyzed by comparing different levels of penicillin resistance, and the assay can be performed under 0.5% butanol, a stress condition thought to be physiologically relevant.
Conclusions:
The β-lactamase PCA system faithfully reports chaperone-substrate interactions in the bacterial cell envelope, and therefore this system has the potential to map the complex protein homeostasis network under a fluctuating environment.

