9E7U

Cryo-EM structure of NOT1:NOT8:PieF

Summary for 9E7U

• Entry DOI: 10.2210/pdb9e7u/pdb
• EMDB information: 47690
• Descriptor: Ubiquitin-like protein SMT3,CCR4-NOT transcription complex subunit 8, Dot/Icm T4SS effector PieF, CCR4-NOT transcription complex subunit 1, ... (5 entities in total)
• Functional Keywords: pief, mrna decay, deadenylation, ccr4-not, host-pathogen interactions, gene regulation
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 93585.38

Authors

Levdansky, E.,Deme, J.,Lea, S.M.,Valkov, E. (deposition date: 2024-11-04, release date: 2025-07-23)

Primary citation

Levdansky, Y.,Deme, J.C.,Turner, D.J.,Piczak, C.T.,Pekovic, F.,Valkov, A.L.,Tarasov, S.G.,Lea, S.M.,Valkov, E.
Intracellular pathogen effector reprograms host gene expression by inhibiting mRNA decay.
Nat Commun, 16:6452-6452, 2025

PubMed Abstract: Legionella pneumophila, an intracellular bacterial pathogen, injects effector proteins into host cells to manipulate cellular processes and promote its survival and proliferation. Here, we reveal a unique mechanism by which the Legionella effector PieF perturbs host mRNA decay by targeting the human CCR4-NOT deadenylase complex. High-resolution cryo-electron microscopy structures and biochemical analyses reveal that PieF binds with nanomolar affinity to the NOT7 and NOT8 catalytic subunits of CCR4-NOT, obstructing RNA access and displacing a catalytic Mg²⁺ ion from the active site. Additionally, PieF prevents NOT7/8 from associating with their partner deadenylases NOT6/6L, inhibiting the assembly of a functional deadenylase complex. Consequently, PieF robustly blocks mRNA poly(A) tail shortening and degradation with striking potency and selectivity for NOT7/8. This inhibition of deadenylation by PieF impedes cell cycle progression in human cells, revealing a novel bacterial strategy to modulate host gene expression.

PubMed: 40651939
DOI: 10.1038/s41467-025-61194-2

Experimental method

ELECTRON MICROSCOPY (3.5 Å)