6C90

Human Mtr4 helicase in complex with ZCCHC8-CTD

Summary for 6C90

• Entry DOI: 10.2210/pdb6c90/pdb
• Descriptor: Exosome RNA helicase MTR4,Exosome RNA helicase MTR4, Zinc finger CCHC domain-containing protein 8, ADENOSINE-5'-DIPHOSPHATE, ... (7 entities in total)
• Functional Keywords: hydrolase, next, exosome, nucleotide-binding, atpase, rna, helicase, translocase, rna binding protein, hydrolase-rna binding protein complex, hydrolase/rna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 90110.50

Authors

Puno, M.R.,Lima, C.D. (deposition date: 2018-01-25, release date: 2018-05-30, Last modification date: 2023-10-04)

Primary citation

Puno, M.R.,Lima, C.D.
Structural basis for MTR4-ZCCHC8 interactions that stimulate the MTR4 helicase in the nuclear exosome-targeting complex.
Proc. Natl. Acad. Sci. U.S.A., 115:E5506-E5515, 2018

PubMed Abstract: The nuclear exosome-targeting (NEXT) complex functions as an RNA exosome cofactor and is involved in surveillance and turnover of aberrant transcripts and noncoding RNAs. NEXT is a ternary complex composed of the RNA-binding protein RBM7, the scaffold zinc-knuckle protein ZCCHC8, and the helicase MTR4. While RNA interactions with RBM7 are known, it remains unclear how NEXT subunits collaborate to recognize and prepare substrates for degradation. Here, we show that MTR4 helicase activity is enhanced when associated with RBM7 and ZCCHC8. While uridine-rich substrates interact with RBM7 and are preferred, optimal activity is observed when substrates include a polyadenylated 3' end. We identify a bipartite interaction of ZCCHC8 with MTR4 and uncover a role for the conserved C-terminal domain of ZCCHC8 in stimulating MTR4 helicase and ATPase activities. A crystal structure reveals that the ZCCHC8 C-terminal domain binds the helicase core in a manner that is distinct from that observed for exosome cofactors Trf4p and Air2p. Our results are consistent with a model whereby effective targeting of substrates by NEXT entails recognition of elements within the substrate and activation of MTR4 helicase activity.

PubMed: 29844170
DOI: 10.1073/pnas.1803530115

Experimental method

X-RAY DIFFRACTION (2.2 Å)