المؤلفون: Bastidas, Robert J., Kędzior, Mateusz, Davidson, Robert K., Walsh, Stephen C., Dolat, Lee, Sixt, Barbara Susanne, Pruneda, Jonathan N., Coers, Jörn, Valdivia, Raphael H.

المصدر: eLIFE. 12

مصطلحات موضوعية: acetylase, bacterial effectors, bacterial host exit, Chlamydia trachomatis, deubiquitinase, infectious disease, microbiology, ubiquitin

الوصف: Many cellular processes are regulated by ubiquitin-mediated proteasomal degradation. Pathogens can regulate eukaryotic proteolysis through the delivery of proteins with de-ubiquitinating (DUB) activities. The obligate intracellular pathogen Chlamydia trachomatis secretes Cdu1 (ChlaDUB1), a dual deubiquitinase and Lys-acetyltransferase, that promotes Golgi remodeling and survival of infected host cells presumably by regulating the ubiquitination of host and bacterial proteins. Here, we determined that Cdu1's acetylase but not its DUB activity is important to protect Cdu1 from ubiquitin-mediated degradation. We further identified three C. trachomatis proteins on the pathogen-containing vacuole (InaC, IpaM, and CTL0480) that required Cdu1's acetylase activity for protection from degradation and determined that Cdu1 and these Cdu1-protected proteins are required for optimal egress of Chlamydia from host cells. These findings highlight a non-canonical mechanism of pathogen-mediated protection of virulence factors from degradation after their delivery into host cells and the coordinated regulation of secreted effector proteins.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-221552Test
https://doi.org/10.7554/eLife.87386Test
https://umu.diva-portal.org/smash/get/diva2:1842736/FULLTEXT01.pdfTest

المؤلفون: Witting, Katharina, Berlin, Ilana, Pruneda, Jonathan N., Wu, Kuen-Phon, Chang, Jer-Gung, Bialas, Johanna, Groettrup, Marcus, El Oualid, Farid, Ovaa, Huib, Mulder, Monique P. C.

الوصول الحر: https://www.europeana.eu/item/2048441/item_POR44HKEVKENLRQQU25QQUJRDUHGDFLN?utm_source=api&utm_medium=api&utm_campaign=YuvuWBeCaTest

المؤلفون: Lobato-Márquez, Damián, Conesa, José Javier, López-Jiménez, Ana Teresa, Divine, Michael E, Pruneda, Jonathan N, Mostowy, Serge

الوصف: During host cell invasion, Shigella escapes to the cytosol and polymerizes actin for cell-to-cell spread. To restrict cell-to-cell spread, host cells employ cell-autonomous immune responses including antibacterial autophagy and septin cage entrapment. How septins interact with the autophagy process to target Shigella for destruction is poorly understood. Here, we employed a correlative light and cryo-soft X-ray tomography (cryo-SXT) pipeline to study Shigella septin cage entrapment in its near-native state. Quantitative cryo-SXT showed that Shigella fragments mitochondria and enabled visualization of X-ray-dense structures (∼30 nm resolution) surrounding Shigella entrapped in septin cages. Using Airyscan confocal microscopy, we observed lysine 63 (K63)-linked ubiquitin chains decorating septin-cage-entrapped Shigella. Remarkably, septins and K63 chains are present in separate bacterial microdomains, indicating they are recruited separately during antibacterial autophagy. Cryo-SXT and live-cell imaging revealed an interaction between septins and LC3B-positive membranes during autophagy of Shigella. Together, these findings demonstrate how septin-caged Shigella are targeted for autophagy and provide fundamental insights into autophagy-cytoskeleton interactions.

وصف الملف: text

العلاقة: https://researchonline.lshtm.ac.uk/id/eprint/4669934/1/Marquez-etal-2023-Septins-and-k63-ubiquitin-chains.pdfTest; Lobato-Márquez, Damián; Conesa, José Javier; López-Jiménez, Ana Teresa; Divine, Michael E; Pruneda, Jonathan N; Mostowy, Serge ; (2023) Septins and K63 ubiquitin chains are present in separate bacterial microdomains during autophagy of entrapped Shigella. Journal of cell science, 136 (7). jcs261139-. ISSN 0021-9533 DOI: https://doi.org/10.1242/jcs.261139Test

الإتاحة: https://doi.org/10.1242/jcs.261139Test
https://researchonline.lshtm.ac.uk/id/eprint/4669934Test/
https://researchonline.lshtm.ac.uk/id/eprint/4669934/1/Marquez-etal-2023-Septins-and-k63-ubiquitin-chains.pdfTest

المؤلفون: Pan, Xueyang, Alvarez, Albert N, Ma, Mengqi, Lu, Shenzhao, Crawford, Michael W, Briere, Lauren C, Kanca, Oguz, Yamamoto, Shinya, Sweetser, David A, Wilson, Jenny L, Napier, Ruth J, Pruneda, Jonathan N, Bellen, Hugo J

المساهمون: Office of Research Infrastructure Programs, National Institutes of Health, Huffington Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, OHSU Molecular Microbiology and Immunology Interdisciplinary Pilot Award, National Center for Advancing Translational Sciences, National Institute of General Medical Sciences, U.S. Department of Veterans Affairs, Office of Strategic Coordination, Hill Family Fund for the Diagnosis, Management of Rare and Undiagnosed Diseases at Mass General, American Institute for Neuro Integrative Development Inc

المصدر: eLife ; volume 12 ; ISSN 2050-084X

الوصف: Protein UFMylation downstream of the E1 enzyme UBA5 plays essential roles in development and endoplasmic reticulum stress. Variants in the UBA5 gene are associated with developmental and epileptic encephalopathy 44 (DEE44), an autosomal recessive disorder characterized by early-onset encephalopathy, movement abnormalities, global developmental delay, intellectual disability, and seizures. DEE44 is caused by at least 12 different missense variants described as loss of function (LoF), but the relationships between genotypes and molecular or clinical phenotypes remain to be established. We developed a humanized UBA5 fly model and biochemical activity assays in order to describe in vivo and in vitro genotype–phenotype relationships across the UBA5 allelic series. In vivo, we observed a broad spectrum of phenotypes in viability, developmental timing, lifespan, locomotor activity, and bang sensitivity. A range of functional effects was also observed in vitro across comprehensive biochemical assays for protein stability, ATP binding, UFM1 activation, and UFM1 transthiolation. Importantly, there is a strong correlation between in vivo and in vitro phenotypes, establishing a classification of LoF variants into mild, intermediate, and severe allelic strengths. By systemically evaluating UBA5 variants across in vivo and in vitro platforms, this study provides a foundation for more basic and translational UBA5 research, as well as a basis for evaluating current and future individuals afflicted with this rare disease.

الإتاحة: https://doi.org/10.7554/elife.89891.3Test
https://cdn.elifesciences.org/articles/89891/elife-89891-v1.pdfTest
https://cdn.elifesciences.org/articles/89891/elife-89891-v1.xmlTest
https://elifesciences.org/articles/89891Test

المؤلفون: Lobato-Márquez, Damián, Javier Conesa, José, López-Jiménez, Ana Teresa, Divine, Michael E., Pruneda, Jonathan N., Mostowy, Serge

المساهمون: HORIZON EUROPE European Research Council, National Institute of General Medical Sciences, Atracción de Talento, Wellcome Trust

المصدر: Autophagy Reports ; volume 2, issue 1 ; ISSN 2769-4127

الإتاحة: https://doi.org/10.1080/27694127.2023.2213541Test

المؤلفون: Franklin, Tyler G., Brzovic, Peter S., Pruneda, Jonathan N.

المصدر: Molecular Cell ; volume 83, issue 24, page 4538-4554.e4 ; ISSN 1097-2765

مصطلحات موضوعية: Cell Biology, Molecular Biology

الإتاحة: https://doi.org/10.1016/j.molcel.2023.11.017Test
https://api.elsevier.com/content/article/PII:S1097276523009620?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1097276523009620?httpAccept=text/plainTest

المؤلفون: Warren, Gus D., Kitao, Tomoe, Franklin, Tyler G., Nguyen, Justine V., Geurink, Paul P., Kubori, Tomoko, Nagai, Hiroki, Pruneda, Jonathan N.

المساهمون: National Institutes of Health, Japan Society for the Promotion of Science, U.S. Department of Energy, Ministry of Education, Culture, Sports, Science and Technology, National Institute of General Medical Sciences, Collins Medical Trust, Takeda Science Foundation, Oregon Health and Science University

المصدر: Molecular Cell ; volume 83, issue 1, page 105-120.e5 ; ISSN 1097-2765

مصطلحات موضوعية: Cell Biology, Molecular Biology

الإتاحة: https://doi.org/10.1016/j.molcel.2022.11.022Test
https://api.elsevier.com/content/article/PII:S1097276522011352?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1097276522011352?httpAccept=text/plainTest

المؤلفون: Szczesna, Magdalena, Huang, Yizhou, Lacoursiere, Rachel E, Bonini, Francesca, Pol, Vito, Koc, Fulya, Ward, Beatrice, Geurink, Paul P, Pruneda, Jonathan N, Thurston, Teresa L M

المصدر: Cell Host Microbe ; ISSN:1934-6069 ; Volume:32 ; Issue:6

مصطلحات موضوعية: Autophagy, Burkholderia, RNF213, TssM, Ubiquitin esterase, bacterial effector, cell-autonomous immunity, non-canonical ubiquitylation

الوصف: Aspects of how Burkholderia escape the host's intrinsic immune response to replicate in the cell cytosol remain enigmatic. Here, we show that Burkholderia has evolved two mechanisms to block the activity of Ring finger protein 213 (RNF213)-mediated non-canonical ubiquitylation of bacterial lipopolysaccharide (LPS), thereby preventing the initiation of antibacterial autophagy. First, Burkholderia's polysaccharide capsule blocks RNF213 association with bacteria and second, the Burkholderia deubiquitylase (DUB), TssM, directly reverses the activity of RNF213 through a previously unrecognized esterase activity. Structural analysis provides insight into the molecular basis of TssM esterase activity, allowing it to be uncoupled from its isopeptidase function. Furthermore, a putative TssM homolog also displays esterase activity and removes ubiquitin from LPS, establishing this as a virulence mechanism. Of note, we also find that additional immune-evasion mechanisms exist, revealing that overcoming this arm of the host's immune response is critical to the pathogen.

العلاقة: https://doi.org/10.1016/j.chom.2024.04.012Test; https://pubmed.ncbi.nlm.nih.gov/38870903Test

الإتاحة: https://doi.org/10.1016/j.chom.2024.04.012Test
https://pubmed.ncbi.nlm.nih.gov/38870903Test

المؤلفون: Bastidas, Robert J., Kędzior, Mateusz, Davidson, Robert K., Walsh, Stephen C., Dolat, Lee, Sixt, Barbara S., Pruneda, Jonathan N., Coers, Jörn, Valdivia, Raphael H.

الإتاحة: https://doi.org/10.7554/elife.87386.2.sa4Test

المؤلفون: Bastidas, Robert J, Kędzior, Mateusz, Davidson, Robert K, Walsh, Stephen C, Dolat, Lee, Sixt, Barbara S, Pruneda, Jonathan N, Coers, Jorn, Valdivia, Raphael H

المساهمون: Kana, Bavesh D

الإتاحة: https://doi.org/10.7554/elife.87386.3.sa4Test