8UIC

Structure of the Drosophila IntS11-CG7044(dBRAT1) complex

Summary for 8UIC

• Entry DOI: 10.2210/pdb8uic/pdb
• EMDB information: 42291 42292
• Descriptor: Integrator complex subunit 11, FI02071p, ZINC ION (3 entities in total)
• Functional Keywords: complex, chaperone, nuclease, rna binding protein
• Biological source: Drosophila melanogaster (fruit fly); More
• Total number of polymer chains: 2
• Total formula weight: 180966.44

Authors

Lin, M.,Tong, L. (deposition date: 2023-10-10, release date: 2024-08-21)

Primary citation

Lin, M.H.,Jensen, M.K.,Elrod, N.D.,Chu, H.F.,Haseley, M.,Beam, A.C.,Huang, K.L.,Chiang, W.,Russell, W.K.,Williams, K.,Proschel, C.,Wagner, E.J.,Tong, L.
Cytoplasmic binding partners of the Integrator endonuclease INTS11 and its paralog CPSF73 are required for their nuclear function.
Mol.Cell, 84:2900-2917.e10, 2024

PubMed Abstract: INTS11 and CPSF73 are metal-dependent endonucleases for Integrator and pre-mRNA 3'-end processing, respectively. Here, we show that the INTS11 binding partner BRAT1/CG7044, a factor important for neuronal fitness, stabilizes INTS11 in the cytoplasm and is required for Integrator function in the nucleus. Loss of BRAT1 in neural organoids leads to transcriptomic disruption and precocious expression of neurogenesis-driving transcription factors. The structures of the human INTS9-INTS11-BRAT1 and Drosophila dIntS11-CG7044 complexes reveal that the conserved C terminus of BRAT1/CG7044 is captured in the active site of INTS11, with a cysteine residue directly coordinating the metal ions. Inspired by these observations, we find that UBE3D is a binding partner for CPSF73, and UBE3D likely also uses a conserved cysteine residue to directly coordinate the active site metal ions. Our studies have revealed binding partners for INTS11 and CPSF73 that behave like cytoplasmic chaperones with a conserved impact on the nuclear functions of these enzymes.

PubMed: 39032490
DOI: 10.1016/j.molcel.2024.06.017

Experimental method

ELECTRON MICROSCOPY (3.54 Å)