Review
Biochemistry & Molecular Biology
Sahel Amoozadeh, Jodie Johnston, Claudia-Nicole Meisrimler
Summary: Interactions between pathogenic fungi and oomycetes with plants can have different impacts on plant health, with effector proteins playing a key role in successful colonization of the host plant. Investigating the biological and functional roles of effectors through bioinformatics and experimental approaches is crucial for understanding plant-microbe interactions. The use of next generation protein modeling software like RoseTTafold and AlphaFold2, which utilize novel machine-learning algorithms, has advanced the field of effector biology and made these methods more accessible to users.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Katherine Oravecz-Wilson, Corinne Rossi, Cynthia Zajac, Yaping Sun, Lu Li, Thomas Decoville, Hideaki Fujiwara, Stephanie Kim, Daniel Peltier, Pavan Reddy
Summary: Autophagy plays a crucial role in regulating allo-immunity in T cells by affecting proliferation and effector functions. ATG5-dependent autophagy can reduce GVHD while maintaining GVT responses in transplantation settings.
Article
Biochemistry & Molecular Biology
Kuo Zhang, Ting Peng, Xinyuan Tao, Miao Tian, Yanxin Li, Zhao Wang, Shuaifei Ma, Shufan Hu, Xing Pan, Juan Xue, Jiwei Luo, Qiulan Wu, Yang Fu, Shan Li
Summary: This study reveals the multistep enzymatic mechanism of CopC-catalyzed arginine ADPR deacylization in resisting bacterial infections, providing a structural framework for understanding the molecular basis of this process.
Review
Immunology
Guodong Zhou, Yuying Zhao, Qifeng Ma, Quan Li, Shifeng Wang, Huoying Shi
Summary: Salmonella is a dangerous bacterial species that can cause various diseases in humans and animals. This review discusses the mechanisms used by Salmonella to evade or manipulate the host immune defenses at different levels. The effector proteins delivered by the secretory systems play a key role in Salmonella's strategies against host defense mechanisms. Salmonella manipulates inflammatory pathways, ubiquitination, and autophagy processes to survive and replicate in the host.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Pooja Pandey, Alexandre Y. Leary, Yasin Tumtas, Zachary Savage, Bayantes Dagvadorj, Cian Duggan, Enoch L. H. Yuen, Nattapong Sanguankiattichai, Emily Tan, Virendrasinh Khandare, Amber J. Connerton, Temur Yunusov, Mathias Madalinski, Federico Gabriel Mirkin, Sebastian Schornack, Yasin Dagdas, Sophien Kamoun, Tolga O. Bozkurt
Summary: The effector protein PexRD54 secreted by the Irish famine pathogen Phytophthora infestans can induce autophagosome formation and promote the generation of autophagosomes by utilizing lipid droplets through specific trafficking pathways. This effector protein mimics starvation-induced autophagy to alter endomembrane trafficking at the host-pathogen interface, facilitating colonization by the pathogen.
Article
Chemistry, Multidisciplinary
David E. Clarke, Guanglu Wu, Ce Wu, Oren A. Scherman
Summary: Control of spatial and temporal behavior of peptide segments is crucial in fabricating functional peptide-based materials and nanostructures. Complex sequence design and inclusion of unnatural amino acids or synthetic modifications are often required to achieve desired structures. In this study, the structural properties of 1:1 inclusion complexes between specific oligopeptides and CB[8] were investigated, showing induction of turns and tunable structural chirality by altering peptide sequences. Extension of peptide sequence binding with CB[8] was also explored as a simple method to construct a peptide hairpin.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Dennis Quentin, Jan S. Schuhmacher, Bjoern U. Klinkh, Jeni Lauer, Tanvir R. Shaikh, Pim J. Huis in 't Veld, Luisa M. Welp, Henning Urlaub, Marino Zerial, Stefan Raunser
Summary: This study determines the cryo-EM structure of human FERRY, which has a unique clamp-like architecture distinct from other Rab effectors. Functional and mutational studies reveal that the C-terminal coiled-coil of Fy-2 acts as the binding region for Fy-1/3 and Rab5, while both coiled-coils and Fy-5 are involved in mRNA binding. Mutations causing truncations of Fy-2 in patients with neurological disorders impair Rab5 binding or FERRY complex assembly. Fy-2 serves as a binding hub that connects all five complex subunits and mediates the binding to mRNA and early endosomes via Rab5. The study provides mechanistic insights into long-distance mRNA transport and introduces a new mode of RNA binding involving coiled-coil domains.
Article
Multidisciplinary Sciences
Khuram U. Ashraf, Rie Nygaard, Owen N. Vickery, Satchal K. Erramilli, Carmen M. Herrera, Thomas H. McConville, Vasileios I. Petrou, Sabrina I. Giacometti, Meagan Belcher Dufrisne, Kamil Nosol, Allen P. Zinkle, Chris L. B. Graham, Michael Loukeris, Brian Kloss, Karolina Skorupinska-Tudek, Ewa Swiezewska, David I. Roper, Oliver B. Clarke, Anne-Catrin Uhlemann, Anthony A. Kossiakoff, M. Stephen Trent, Phillip J. Stansfeld, Filippo Mancia
Summary: This study presents the structures of WaaL from Cupriavidus metallidurans and provides molecular details and a mechanistic model for lipopolysaccharide maturation.
Review
Immunology
Priya Bhatnagar, Gopinathan Pillai Sreekanth, Kaja Murali-Krishna, Anmol Chandele, Ramakrishnan Sitaraman
Summary: This review article discusses the role of Dengue virus non-structural protein 5 (NS5) and its interactions with other proteins in the human host, particularly focusing on its interference with anti-viral interferon signaling. By annotating and consolidating known and potential NS5 interactors using experimental and computational approaches, the study provides insights for further research efforts to understand how NS5 manipulates the human-virus interface and immune responses.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Plant Sciences
Xinyu Lu, Zitong Yang, Wen Song, Jinlu Miao, Hanqing Zhao, Peiyun Ji, Tianli Li, Jierui Si, Zhiyuan Yin, Maofeng Jing, Danyu Shen, Daolong Dou
Summary: In this study, a class of FYVE domain-containing proteins was systematically investigated, and one secreted protein, PsFYVE1, was found to promote Phytophthora infection in both tobacco and soybean. It was also discovered that PsFYVE1 and NbRZ-1A co-regulated pre-mRNA alternative splicing and transcription levels of plant immunity-related genes, promoting disease development.
Article
Microbiology
Zhifeng Zeng, Yu Chen, Rafael Pinilla-Redondo, Shiraz A. Shah, Fen Zhao, Chen Wang, Zeyu Hu, Chang Wu, Changyi Zhang, Rachel J. Whitaker, Qunxin She, Wenyuan Han
Summary: This study reveals a short pAgo protein in the archaeon Sulfolobus islandicus, along with its genetically associated proteins Aga1 and Aga2, provide robust anti-viral protection through abortive infection. Aga2 is a toxic transmembrane effector that binds anionic phospholipids, resulting in membrane depolarization and cell killing. Ago and Aga1 form a stable complex with nucleic acid-directed recognition ability and directly interact with Aga2, suggesting an immune sensing mechanism.
CELL HOST & MICROBE
(2022)
Article
Multidisciplinary Sciences
Tao-Tao Chen, Yanling Lin, Shijun Zhang, Shuxin Liu, Lei Song, Wenhong Zhong, Zhao-Qing Luo, Aidong Han
Summary: The intracellular bacterial pathogen Legionella pneumophila hijacks host vesicular transport factor p115 to localize its effector protein LegA15 in host lipid droplets (LDs) and causes fragmentation of host Golgi apparatus. LegA15 is an atypical GTPase that modulates host LD homeostasis through its GTPase activity.
Article
Biochemistry & Molecular Biology
Vincent D. Maciej, Nevena Mateva, Juliane Schwarz, Theresa Dittmers, Megha Mallick, Henning Urlaub, Sutapa Chakrabarti
Summary: The study reveals a weak interaction between the RNA-binding protein TTP and the decapping enzyme DCP2, which affects the stability of transcripts containing AU-rich elements (AREs). The interaction involves disordered regions of both proteins and leads to the assembly of phase-separated droplets. These findings highlight the significance of weak interactions in cellular functionality.
NUCLEIC ACIDS RESEARCH
(2022)
Editorial Material
Biochemistry & Molecular Biology
Timothy L. Cover
Summary: A split luciferase assay was developed to monitor the T4SS-mediated translocation of CagA into host cells in real-time, facilitating the quantitative analysis of CagA translocation and the kinetics of its delivery. This system also confirmed the importance of protein unfolding for secretion by the Cag T4SS.
MOLECULAR MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yugo Kitazawa, Nozomu Iwabuchi, Kensaku Maejima, Momoka Sasano, Oki Matsumoto, Hiroaki Koinuma, Ryosuke Tokuda, Masato Suzuki, Kenro Oshima, Shigetou Namba, Yasuyuki Yamaji
Summary: Phyllogen, a bacterial effector produced by pathogenic phytoplasma, targets host proteins for proteasomal degradation by mediating their interaction with proteasome shuttle proteins instead of ubiquitin. In this process, RAD23 shuttle proteins recruit ubiquitinated proteins to the proteasome. Phyllogen directly mediates interaction between MTF and RAD23, inducing the proteasomal degradation of MTF.
Article
Biochemistry & Molecular Biology
Andrea Gubas, Ivan Dikic
Summary: Autophagy is a highly conserved cellular process for degrading abnormal cellular components and foreign pathogens, which can be selective or nonselective. Autophagy receptors play a crucial role in linking and degrading cell components during autophagy, undergoing structural modifications to fulfill their function.
Article
Biochemistry & Molecular Biology
Benedikt Linder, Caterina Klein, Marina E. Hoffmann, Florian Bonn, Ivan Dikic, Donat Koegel
Summary: By regulating hallmarks of cancer, BAG3 plays oncogenic roles in various malignant diseases, and its knockdown enhances ciliogenesis and reduces cell migration.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Cristian Prieto-Garcia, Oliver Hartmann, Michaela Reissland, Thomas Fischer, Carina R. Maier, Mathias Rosenfeldt, Christina Schuelein-Voelk, Kevin Klann, Reinhard Kalb, Ivan Dikic, Christian Munch, Markus E. Diefenbacher
Summary: Squamous cell carcinomas (SCC) exhibit high mutational burden and platinum-based chemotherapy resistance, with increased Np63 expression associated with resistance; USP28 is recruited to sites of DNA damage and plays a regulatory role in DNA damage repair in SCC; Targeting the USP28- increment Np63 axis can overcome chemotherapy resistance in SCC.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biotechnology & Applied Microbiology
Evgenij Fiskin, Caleb A. Lareau, Leif S. Ludwig, Gokcen Eraslan, Feimei Liu, Aaron M. Ring, Ramnik J. Xavier, Aviv Regev
Summary: The study introduces a novel method called PHAGE-ATAC for simultaneous single-cell measurements of protein levels and chromatin accessibility profiles, using mitochondrial DNA-based clonal tracing. PHAGE-ATAC is utilized for multimodal analysis in primary human immune cells, sample multiplexing, intracellular protein analysis, and detection of SARS-CoV-2 spike protein. Additionally, a synthetic high-complexity phage library is constructed for selection of antigen-specific nanobodies, enabling protein detection, cell characterization, and screening with single-cell genomics.
NATURE BIOTECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Andrea Gubas, Ivan Dikic
Summary: The endoplasmic reticulum (ER) is involved in many essential cellular processes, including ER-phagy. ER-phagy is a process that selectively degrades ER fragments to maintain ER size and morphology, and it relies on specialized ER-shaping proteins. This review provides insights into the membrane remodeling mechanisms of ER-phagy and emphasizes its significance in human physiology and pathology.
Article
Microbiology
Varnesh Tiku, Chun Kew, Eric M. Kofoed, Yutian Peng, Ivan Dikic, Man-Wah Tan
Summary: This study reveals that A. baumannii secretes an inflammatory bioactive lipid that activates multiple pro-inflammatory signaling pathways and induces cell death. This finding contributes to a better understanding of the immune mechanisms involved in A. baumannii infection.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Cell Biology
Ivan Dikic, Brenda A. Schulman
Summary: Recent studies have advanced our understanding of ubiquitylation, revealing unconventional ubiquitylation mechanisms used by pathogens to promote infection. Structural studies have shown that ubiquitin functions involve complex multivalent interactions that regulate transcription or protein degradation. Furthermore, these interactions can induce conformational changes and regulate protein degradation or transcription. These newly discovered mechanisms provide potential opportunities for innovative therapeutic interventions for diseases such as cancer and infectious diseases.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Daniela S. Krause, Ivan Dikic
Article
Cell Biology
Alexandra Hertel, Ludovico Martins Alves, Henrik Dutz, Georg Tascher, Florian Bonn, Manuel Kaulich, Ivan Dikic, Stefan Eimer, Florian Steinberg, Anja Bremm
Summary: This study revealed a mechanism of controlling mTORC1 activation cascade at lysosomes through USP32-regulated LAMTOR1 ubiquitination.
Article
Chemistry, Multidisciplinary
David A. Perez A. Berrocal, Thimmalapura M. Vishwanatha, Daniel Horn-Ghetko, J. Josephine Botsch, Laura A. Hehl, Sebastian Kostrhon, Mohit Misra, Ivan Dikic, Paul P. Geurink, Hans van Dam, Brenda A. Schulman, Monique P. C. Mulder
Summary: Protein post-translational modification with ubiquitin (Ub) is a versatile signal regulating cell biology, and diseases associated with impaired Ub modification present opportunities for novel targeted treatments. The final components of the ubiquitination cascade, E3 ligases, have potential as small molecule targets. UbSRhodol, an autoimmolative Ub-based probe, enables detection of changes in E3 transthiolation activity, making it suitable for high-throughput screening and identification of small molecules modulating E3 activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Editorial Material
Biochemistry & Molecular Biology
Angus I. Lamond, Ivan Dikic, Andre Nussenzweig, Christoph W. Mueller, Janet M. Thornton, Michael B. Yaffe
Article
Cell Biology
Anshu Bhattacharya, Rukmini Mukherjee, Santosh Kumar Kuncha, Melinda Elaine Brunstein, Rajeshwari Rathore, Stephan Junek, Christian Muench, Ivan Dikic
Summary: Acute lysosomal membrane damage reduces functional lysosomes, but they have a recovery potential independent of lysosomal biogenesis and remain unaffected in cells depleted in TFEB and TFE3. A lysosomal membrane regeneration pathway was discovered that depends on ATG8, LIMP2, TBC1D15, dynamin-2, kinesin-5B, and clathrin. LIMP2 acts as a lysophagy receptor, binding ATG8, which recruits TBC1D15 to damaged lysosomal membranes. TBC1D15 interacts with ATG8 proteins and stabilizes the autophagic lysosomal reformation machinery, promoting lysosomal tubule formation and dynamin-2-dependent scission.
NATURE CELL BIOLOGY
(2023)
Review
Immunology
Joao Mello-Vieira, Tobias Bopp, Ivan Dikic
Summary: Cell-autonomous immunity is the first line of defense for cells to recognize and eliminate invasive pathogens. Ubiquitination plays a crucial role in orchestrating immune signaling networks and stimulating the appropriate immune response. This review focuses on how ubiquitin connects pathogen sensing pathways to cellular responses and discusses therapeutic options for enhancing cell-autonomous immune responses.
CURRENT OPINION IN IMMUNOLOGY
(2023)
Article
Cell Biology
Alexis Gonzalez, Ivan Dikic
Meeting Abstract
Oncology
Alicia Haydo, Johanna Ertl, Jennifer Schmidt, Marina E. Hoffmann, Stephanie Hehlgans, Alisha Crider, Rajeshwari Rathore, Christel Herold-Mende, Ivan Dikic, Mingji Dai, Alexander Adibekian, Franz Roedel, Donat Koegel, Benedikt Linder
STRAHLENTHERAPIE UND ONKOLOGIE
(2023)