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9VD9

Cryo-EM structure of the human DSS1-INTAC-PEC complex

This is a non-PDB format compatible entry.
Summary for 9VD9
Entry DOI10.2210/pdb9vd9/pdb
EMDB information39339
Descriptor26S proteasome complex subunit SEM1, Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform, Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform, ... (41 entities in total)
Functional Keywordsdss1, integrator, intac, transcription
Biological sourceHomo sapiens (human)
More
Total number of polymer chains38
Total formula weight2065239.01
Authors
Zheng, H.,Xu, Y.,Cheng, J. (deposition date: 2025-06-07, release date: 2025-06-25, Last modification date: 2025-10-15)
Primary citationXu, C.,Zhou, Q.X.,Zheng, H.,Song, A.,Zhao, W.Y.,Xu, T.T.,Xiong, Y.,Zhang, Y.J.,Huang, Z.,Xu, Y.,Cheng, J.,Chen, F.X.
DSS1 is required for proper Integrator-PP2A function.
Nat Commun, 16:6206-6206, 2025
Cited by
PubMed Abstract: Integrator-PP2A (INTAC) is a highly modular complex orchestrating the transition of paused RNA polymerase II into productive elongation or promoter-proximal premature termination, with its loss resulting in transcription dysregulation and genome instability. Here, we identify human DSS1-a flexible 70-residue protein found in multiple functionally diverse complexes including the 26S proteasome-as an integral subunit of the INTAC backbone. Structural analysis of DSS1-INTAC, both alone and in association with paused polymerase, demonstrates intimate interactions between DSS1 and the INTAC backbone. We identify tryptophan 39 of DSS1 as being critical for interacting with INTAC and find that its mutation disrupts DSS1's interaction with INTAC, while maintaining DSS1's interaction with the proteasome. This substitution not only impairs INTAC-dependent transcriptional regulation, but also reveals that INTAC is DSS1's major chromatin-bound form. Together, our findings reveal a role for DSS1 in supporting the structure and regulatory functions of INTAC.
PubMed: 40617815
DOI: 10.1038/s41467-025-61257-4
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (4.6 Å)
Structure validation

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