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Updated: May 4, 2026

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
Published on: September 28, 2018
Programmed cell death protein 5 interacts with the cytosolic chaperonin containing tailless complex polypeptide 1
Christopher M Tracy1, Amy J Gray, Jorge Cuéllar
1From the Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602.
Abstract:
Programmed cell death protein 5 (PDCD5) has been proposed to act as a pro-apoptotic factor and tumor suppressor. However, the mechanisms underlying its apoptotic function are largely unknown. A proteomics search for binding partners of phosducin-like protein, a co-chaperone for the cytosolic chaperonin containing tailless complex polypeptide 1 (CCT), revealed a robust interaction between PDCD5 and CCT. PDCD5 formed a complex with CCT and β-tubulin, a key CCT-folding substrate, and specifically inhibited β-tubulin folding. Cryo-electron microscopy studies of the PDCD5·CCT complex suggested a possible mechanism of inhibition of β-tubulin folding. PDCD5 bound the apical domain of the CCTβ subunit, projecting above the folding cavity without entering it. Like PDCD5, β-tubulin also interacts with the CCTβ apical domain, but a second site is found at the sensor loop deep within the folding cavity. These orientations of PDCD5 and β-tubulin suggest that PDCD5 sterically interferes with β-tubulin binding to the CCTβ apical domain and inhibits β-tubulin folding. Given the importance of tubulins in cell division and proliferation, PDCD5 might exert its apoptotic function at least in part through inhibition of β-tubulin folding.
Insights
Programmed cell death protein 5 (PDCD5) inhibits beta-tubulin folding by interacting with the CCT chaperone. This interaction may explain PDCD5's role as a tumor suppressor and pro-apoptotic factor.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Programmed cell death protein 5 (PDCD5) is implicated as a tumor suppressor and pro-apoptotic factor.
- The precise mechanisms of PDCD5's apoptotic function remain largely unelucidated.
- The cytosolic chaperonin containing tailless complex polypeptide 1 (CCT) is essential for protein folding.
Purpose of the Study:
- To investigate the molecular mechanisms by which PDCD5 exerts its pro-apoptotic function.
- To identify binding partners of phosducin-like protein and their role in CCT-mediated protein folding.
Main Methods:
- Proteomics analysis to identify PDCD5-CCT interactions.
- Biochemical assays to assess the effect of PDCD5 on beta-tubulin folding.
- Cryo-electron microscopy to visualize the PDCD5-CCT complex structure.
Main Results:
- PDCD5 was found to interact with CCT and specifically inhibit the folding of its substrate, beta-tubulin.
- Cryo-electron microscopy revealed that PDCD5 binds to the CCTβ apical domain, sterically hindering beta-tubulin binding.
- This steric hindrance suggests a mechanism by which PDCD5 inhibits beta-tubulin folding.
Conclusions:
- PDCD5 inhibits beta-tubulin folding through steric interference with the CCT chaperone.
- This inhibition of beta-tubulin folding likely contributes to PDCD5's role in apoptosis and tumor suppression.
- Targeting tubulin folding represents a potential therapeutic strategy in cancer treatment.
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