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TitleStructure of the catalytic core of the Integrator complex.
Journal, issue, pagesMol Cell, Vol. 81, Issue 6, Page 1246-11259.e8, Year 2021
Publish dateMar 18, 2021
AuthorsMoritz M Pfleiderer / Wojciech P Galej /
PubMed AbstractThe Integrator is a specialized 3' end-processing complex involved in cleavage and transcription termination of a subset of nascent RNA polymerase II transcripts, including small nuclear RNAs (snRNAs) ...The Integrator is a specialized 3' end-processing complex involved in cleavage and transcription termination of a subset of nascent RNA polymerase II transcripts, including small nuclear RNAs (snRNAs). We provide evidence of the modular nature of the Integrator complex by biochemically characterizing its two subcomplexes, INTS5/8 and INTS10/13/14. Using cryoelectron microscopy (cryo-EM), we determined a 3.5-Å-resolution structure of the INTS4/9/11 ternary complex, which constitutes Integrator's catalytic core. Our structure reveals the spatial organization of the catalytic nuclease INTS11, bound to its catalytically impaired homolog INTS9 via several interdependent interfaces. INTS4, a helical repeat protein, plays a key role in stabilizing nuclease domains and other components. In this assembly, all three proteins form a composite electropositive groove, suggesting a putative RNA binding path within the complex. Comparison with other 3' end-processing machineries points to distinct features and a unique architecture of the Integrator's catalytic module.
External linksMol Cell / PubMed:33548203 / PubMed Central
MethodsEM (single particle)
Resolution3.56 - 6.5 Å
Structure data

EMDB-12159:
Structure of the Integrator cleavage module containing INTS4/9/11
Method: EM (single particle) / Resolution: 3.56 Å

EMDB-12163:
Integrator cleavage module with focused classification on the INTS9/11 CTD
Method: EM (single particle) / Resolution: 6.5 Å

EMDB-12164:
Integrator cleavage module with focused classification on the INTS4 CTD
Method: EM (single particle) / Resolution: 6.5 Å

12165

7bfp

EMDB-12165, PDB-7bfp:
Structure of the Integrator cleavage module with INTS4/9/11
Method: EM (single particle) / Resolution: 3.56 Å

12166

7bfq

EMDB-12166: Medium resolution map of the Integrator cleavage module
PDB-7bfq: Structure of the Integrator cleavage module with extended INTS4 and rigid body docked INTS9/11 CTD
Method: EM (single particle) / Resolution: 4.15 Å

Source
  • homo sapiens (human)
KeywordsNUCLEAR PROTEIN / Nuclease / Integrator / 3'-end processing

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