ArticleProceedings of the National Academy of Sciences of the United States of America2012
The molecular basis of ubiquitin-like protein NEDD8 deamidation by the bacterial effector protein Cif.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- Hijacking the Ubl code: bacterial manipulation of ubiquitin-like proteins.Essays in biochemistry · 2025Review
- Ubiquitin-targeted bacterial effectors: rule breakers of the ubiquitin system.The EMBO journal · 2023Review
- Conformational Insights into the Control of CNF1 Toxin Activity by Peptidyl-Prolyl Isomerization: A Molecular Dynamics Perspective.International journal of molecular sciences · 2021Article
- Breaching the Bacterial Envelope: The Pivotal Role of Perforin-2 (MPEG1) Within Phagocytes.Frontiers in immunology · 2021Review
- Bacterial nucleomodulins and cancer: An unresolved enigma.Translational oncology · 2021Review
- Structural insights into the mechanism and inhibition of transglutaminase-induced ubiquitination by the Legionella effector MavC.Nature communications · 2020Article
- Legionella pneumophila regulates the activity of UBE2N by deamidase-mediated deubiquitination.The EMBO journal · 2020Article
- Article
- CNF1-like deamidase domains: common Lego bricks among cancer-promoting immunomodulatory bacterial virulence factors.Pathogens and disease · 2018Review
- Enteric pathogens deploy cell cycle inhibiting factors to block the bactericidal activity of Perforin-2.eLife · 2015Article
- Manual classification strategies in the ECOD database.Proteins · 2015Article
- Integrated Genomics of Crohn's Disease Risk Variant Identifies a Role for CLEC12A in Antibacterial Autophagy.Cell reports · 2015Article
- Review
- Structural and enzymatic characterization of a host-specificity determinant from Salmonella.Acta crystallographica. Section D, Biological crystallography · 2014Article
- Structural and biochemical characterization of the Cop9 signalosome CSN5/CSN6 heterodimer.PloS one · 2014Article
- Article
- What a difference a Dalton makes: bacterial virulence factors modulate eukaryotic host cell signaling systems via deamidation.Microbiology and molecular biology reviews : MMBR · 2013Review
- The cyclomodulin cycle inhibiting factor (CIF) alters cullin neddylation dynamics.The Journal of biological chemistry · 2013Article
- Complex structure of OspI and Ubc13: the molecular basis of Ubc13 deamidation and convergence of bacterial and host E2 recognition.PLoS pathogens · 2013Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
The cycle inhibiting factors (Cifs) are a family of translocated effector proteins, found in diverse pathogenic bacteria, that interfere with the host cell cycle by catalyzing the deamidation of a specific glutamine residue (Gln40) in NEDD8 and the related protein ubiquitin. This modification prevents recycling of neddylated cullin-RING ligases, leading to stabilization of various cullin-RING ligase targets, and also prevents polyubiquitin chain formation. Here, we report the crystal structures of two Cif/NEDD8 complexes, revealing a conserved molecular interface that defines enzyme/substrate recognition. Mutation of residues forming the interface suggests that shape complementarity, rather than specific individual interactions, is a critical feature for complex formation. We show that Cifs from diverse bacteria bind NEDD8 in vitro and conclude that they will all interact with their substrates in the same way. The "occluding loop" in Cif gates access to Gln40 by forcing a conformational change in the C terminus of NEDD8. We used native PAGE to follow the activity of Cif from the human pathogen Yersinia pseudotuberculosis and selected variants, and the position of Gln40 in the active site has allowed us to propose a catalytic mechanism for these enzymes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.