Crystal structure of bacterial cytotoxic necrotizing factor CNF Y reveals molecular building blocks for intoxication
| العنوان: | Crystal structure of bacterial cytotoxic necrotizing factor CNF Y reveals molecular building blocks for intoxication |
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| المؤلفون: | Theresia E.B. Stradal, Paweena Chaoprasid, Wulf Blankenfeldt, Anika Steffen, Thomas Heidler, Petra Dersch, Shuangshuang Dong, Christian Rüter, Sabrina Mühlen, Peer Lukat, Wenjie Bi, Marco Kirchenwitz, Lothar Jänsch, Emerich-Mihai Gazdag |
| المساهمون: | HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. |
| المصدر: | The EMBO Journal e105202 The EMBO journal England |
| بيانات النشر: | EMBO, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | ADP-ribosyl transferase, Protein Conformation, Structural similarity, AB-toxin, ADP‐ribosyl transferase, Bacterial Toxins, Crystallography, X-Ray, Endocytosis, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Cytosol, 0302 clinical medicine, Structural Biology, AB toxin, DUF4765, Tumor Cells, Cultured, Humans, Yersinia pseudotuberculosis, Deamidation, Receptor, Laryngeal Neoplasms, Molecular Biology, 030304 developmental biology, 0303 health sciences, General Immunology and Microbiology, biology, Escherichia coli Proteins, General Neuroscience, Biological Transport, Articles, biology.organism_classification, AB‐toxin, Fusion protein, Yersinia, Microbiology, Virology & Host Pathogen Interaction, Cell biology, CNF, Carcinoma, Squamous Cell, Crystallization, rhoA GTP-Binding Protein, 030217 neurology & neurosurgery |
| الوصف: | Cytotoxic necrotizing factors (CNFs) are bacterial single‐chain exotoxins that modulate cytokinetic/oncogenic and inflammatory processes through activation of host cell Rho GTPases. To achieve this, they are secreted, bind surface receptors to induce endocytosis and translocate a catalytic unit into the cytosol to intoxicate host cells. A three‐dimensional structure that provides insight into the underlying mechanisms is still lacking. Here, we determined the crystal structure of full‐length Yersinia pseudotuberculosis CNFY. CNFY consists of five domains (D1–D5), and by integrating structural and functional data, we demonstrate that D1–3 act as export and translocation module for the catalytic unit (D4–5) and for a fused β‐lactamase reporter protein. We further found that D4, which possesses structural similarity to ADP‐ribosyl transferases, but had no equivalent catalytic activity, changed its position to interact extensively with D5 in the crystal structure of the free D4–5 fragment. This liberates D5 from a semi‐blocked conformation in full‐length CNFY, leading to higher deamidation activity. Finally, we identify CNF translocation modules in several uncharacterized fusion proteins, which suggests their usability as a broad‐specificity protein delivery tool. Structure‐function analyses of the full‐length Yersinia pseudotuberculosis toxin CNFY offer insights into individual domain contributions to stepwise receptor binding, endocytosis, and translocation into the host cell cytosol. |
| تدمد: | 1460-2075 0261-4189 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c62fe8fef11fa48ebc407872f2637c1Test https://doi.org/10.15252/embj.2020105202Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1c62fe8fef11fa48ebc407872f2637c1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602075 02614189 |
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