7CUN

The structure of human Integrator-PP2A complex

Summary for 7CUN

• Entry DOI: 10.2210/pdb7cun/pdb
• EMDB information: 30473
• Descriptor: Integrator complex subunit 1, PP2A-A, PP2A-C, ... (14 entities in total)
• Functional Keywords: integrator-pp2a complex, phosphatase, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 1210278.04

Authors

Zheng, H.,Qi, Y.,Liu, W.,Li, J.,Wang, J.,Xu, Y. (deposition date: 2020-08-23, release date: 2020-11-25, Last modification date: 2025-06-18)

Primary citation

Zheng, H.,Qi, Y.,Hu, S.,Cao, X.,Xu, C.,Yin, Z.,Chen, X.,Li, Y.,Liu, W.,Li, J.,Wang, J.,Wei, G.,Liang, K.,Chen, F.X.,Xu, Y.
Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase.
Science, 370:-, 2020

PubMed Abstract: The 14-subunit metazoan-specific Integrator contains an endonuclease that cleaves nascent RNA transcripts. Here, we identified a complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC), termed INTAC. The 3.5-angstrom-resolution structure reveals that nine human Integrator subunits and PP2A-AC assemble into a cruciform-shaped central scaffold formed by the backbone and shoulder modules, with the phosphatase and endonuclease modules flanking the opposite sides. As a noncanonical PP2A holoenzyme, the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 and thus regulates transcription. Our study extends the function of PP2A to transcriptional regulation and reveals how dual enzymatic activities-RNA cleavage and RNA polymerase II dephosphorylation-are structurally and functionally integrated into the INTAC complex.

PubMed: 33243860
DOI: 10.1126/science.abb5872

Experimental method

ELECTRON MICROSCOPY (3.5 Å)