9E7T
Cryo-EM structure of NOT1:NOT7:PieF
Summary for 9E7T
| Entry DOI | 10.2210/pdb9e7t/pdb |
| EMDB information | 47689 |
| Descriptor | Dot/Icm T4SS effector PieF, CCR4-NOT transcription complex subunit 1, SDH7p Mitochondrial protein involved in assembly of succinate dehydrogenase,CCR4-NOT transcription complex subunit 7, ... (5 entities in total) |
| Functional Keywords | pief, mrna decay, deadenylation, ccr4-not, host-pathogen interactions, gene regulation |
| Biological source | Legionella pneumophila More |
| Total number of polymer chains | 3 |
| Total formula weight | 92965.56 |
| Authors | |
| 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 Cited by 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: 40651939DOI: 10.1038/s41467-025-61194-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.8 Å) |
Structure validation
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