7Z4Z

Human NEXT dimer - focused reconstruction of the dimerization module

Summary for 7Z4Z

• Entry DOI: 10.2210/pdb7z4z/pdb
• Related: 7Z4Y
• EMDB information: 14510 14511
• Descriptor: Zinc finger CCHC domain-containing protein 8, Exosome RNA helicase MTR4 (2 entities in total)
• Functional Keywords: helicase, atpase, rna degradation, exosome, rna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 305982.06

Authors

Gerlach, P.,Lingaraju, M.,Salerno-Kochan, A.,Bonneau, F.,Basquin, J.,Conti, E. (deposition date: 2022-03-06, release date: 2022-06-22, Last modification date: 2024-07-17)

Primary citation

Gerlach, P.,Garland, W.,Lingaraju, M.,Salerno-Kochan, A.,Bonneau, F.,Basquin, J.,Jensen, T.H.,Conti, E.
Structure and regulation of the nuclear exosome targeting complex guides RNA substrates to the exosome.
Mol.Cell, 82:2505-, 2022

PubMed Abstract: In mammalian cells, spurious transcription results in a vast repertoire of unproductive non-coding RNAs, whose deleterious accumulation is prevented by rapid decay. The nuclear exosome targeting (NEXT) complex plays a central role in directing non-functional transcripts to exosome-mediated degradation, but the structural and molecular mechanisms remain enigmatic. Here, we elucidated the architecture of the human NEXT complex, showing that it exists as a dimer of MTR4-ZCCHC8-RBM7 heterotrimers. Dimerization preconfigures the major MTR4-binding region of ZCCHC8 and arranges the two MTR4 helicases opposite to each other, with each protomer able to function on many types of RNAs. In the inactive state of the complex, the 3' end of an RNA substrate is enclosed in the MTR4 helicase channel by a ZCCHC8 C-terminal gatekeeping domain. The architecture of a NEXT-exosome assembly points to the molecular and regulatory mechanisms with which the NEXT complex guides RNA substrates to the exosome.

PubMed: 35688157
DOI: 10.1016/j.molcel.2022.04.011

Experimental method

ELECTRON MICROSCOPY (4 Å)