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Programmed cell death protein 5 interacts with the cytosolic chaperonin containing tailless complex polypeptide 1 (CCT) to regulate ?-tubulin folding.

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 ?-tubulin, a key CCT-folding substrate, and specifically inhibited ?-tubulin folding. Cryo-electron microscopy studies of the PDCD5·CCT complex suggested a possible mechanism of inhibition of ?-tubulin folding. PDCD5 bound the apical domain of the CCT? subunit, projecting above the folding cavity without entering it. Like PDCD5, ?-tubulin also interacts with the CCT? apical domain, but a second site is found at the sensor loop deep within the folding cavity. These orientations of PDCD5 and ?-tubulin suggest that PDCD5 sterically interferes with ?-tubulin binding to the CCT? apical domain and inhibits ?-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 ?-tubulin folding.

SUBMITTER: Tracy CM

PROVIDER: S-EPMC3924310 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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