PDCD5 promotes substrate release from the TRiC complex in cilia and flagella
Year: 2026
Type: article
Abstract: Approximately 10% of eukaryotic proteins are folded by the TRiC/CCT complex (TCP1-ring complex, also called CCT for cytosolic chaperonin containing TCP1), and only open-state TRiC can bind with programmed cell death 5 (PDCD5). However, the physiological role of the PDCD5-TRiC interaction remains elusive. Here, we show that PDCD5 is required for flagellum biogenesis and ciliogenesis and present the PDCD5-TRiC structures in their open states at near-atomic resolution. Mechanically, we find that PDCD5 promotes substrates release by competing with PhLP2A to interact with TRiC, and the depletion of PDCD5 traps flagellum- and cilium-associated proteins within TRiC, finally leading to malformed flagella of spermatids and cilia in mouse ciliated cells. Moreover, we demonstrate that the function of PDCD5 in flagellum biogenesis and ciliogenesis depends on the interaction with TRiC by its C terminus. These findings identify PDCD5 as a TRiC regulator to promote a subset of proteins release.
Source: Molecular Cell
Institutions: Guangzhou Women and Children Medical Center, Guangzhou Medical University, Chinese Academy of Sciences, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, ShenZhen People’s Hospital, Peking University, Shantou University, Shantou University Medical College, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Thermo Fisher Scientific (China), Shanghai Advanced Research Institute, Zhangjiang Laboratory
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
OpenAlex ID: W7118637600