Article
Neurosciences
Mirella A. Hernandez-Lima, Margaret Champion, Zachary Mattiola, Matthias C. Truttmann
Summary: In this study, the researchers investigated how the activity of the AMPylase FIC-1 affects physiological processes in Caenorhabditis elegans. They found that over-expression of FIC-1(E274G) impairs development, fertility, and stress resilience in C. elegans. The study also revealed that FIC-1(E274G) over-expression inhibits pathogen avoidance behavior by suppressing production of specific ligands in sensory neurons.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Amanda K. Casey, Hillery F. Gray, Suneeta Chimalapati, Genaro Hernandez, Andrew T. Moehlman, Nathan Stewart, Hazel A. Fields, Burak Gulen, Kelly A. Servage, Karoliina Stefanius, Aubrie Blevins, Bret M. Evers, Helmut Kramer, Kim Orth
Summary: Protein homeostasis is crucial for cellular health, and imbalanced unfolded protein response (UPR) can lead to inflammation and cellular damage. The enzyme filamentation induced by cyclic-AMP (Fic) modulates UPR response by posttranslational modification of binding immunoglobulin protein (BiP). Loss of Fic affects vision, UPR activation, and stress recovery. This study highlights the importance of Fic-mediated AMPylation in the mammalian pancreas during physiological stress.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Nikolaus Dietz, Markus Huber, Isabel Sorg, Arnaud Goepfert, Alexander Harms, Tilman Schirmer, Christoph Dehio
Summary: The bacterial effector protein Bep1 selectively targets members of the Rac subfamily in the Rho family of small GTPases based on electrostatic interactions, providing a highly selective tool for functional analysis of these GTPases. This study establishes a structural understanding of target selectivity towards Rac-subfamily GTPases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Meili Liu, Zhe Huai, Hongwei Tan, Guangju Chen
Summary: The study investigated the catalytic mechanism of HYPE in AMPylation, revealing a sequential pathway for the transformation of the AMP moiety with BiP and the inhibitory role of glutamate in the process. These findings are inspiring for understanding the catalytic and inhibitory mechanisms of Fic-mediated AMP transfer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Minttu S. Virolainen, Cecilie L. Soltoft, Per A. Pedersen, Lars Ellgaard
Summary: The research team successfully produced full-length FICD by combining a yeast platform and GFP tagging, providing a new approach for optimizing conditions for expression, solubilization, and purification. They also highlighted that this method is not only applicable to FICD, but also to other membrane proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Luke A. A. Perera, David Ron
Summary: The ER-localized Hsp70 chaperone, BiP, undergoes a rapid and reversible modification called AMPylation, which complements the unfolded protein response in regulating protein folding demand in the ER. This modification is mediated by the enzyme FICD, which also has the ability to deAMPylate BiP. The structural basis of BiP recognition by FICD and the potential physiological significance of BiP AMPylation are also discussed.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2023)
Article
Biology
Bothina Mohammed Alharbi, Tahani H. Albinhassan, Razan Ali Alzahrani, Abderrezak Bouchama, Sameer Mohammad, Awatif Abdulaziz Alomari, May Nasser Bin-Jumah, Entissar S. AlSuhaibani, Shuja Shafi Malik
Summary: Rising temperatures and heat waves caused by climate change are detrimental to human health. Exposure to extreme heat during heat waves can cause heat-related illnesses, including heat stroke, which can result in permanent disability. Heat can damage proteins, leading to their misfolding and aggregation, which can be neurotoxic and contribute to neurodegenerative disorders.
Review
Biochemistry & Molecular Biology
Barbara Tedesco, Veronica Ferrari, Marta Cozzi, Marta Chierichetti, Elena Casarotto, Paola Pramaggiore, Francesco Mina, Mariarita Galbiati, Paola Rusmini, Valeria Crippa, Riccardo Cristofani, Angelo Poletti
Summary: Motoneuron diseases (MNDs) are neurodegenerative conditions associated with death of upper and/or lower motoneurons (MNs). Protein misfolding and defects in the protein quality control system are key factors in MND pathogenesis. Heat Shock Protein 70 (HSP70) and small heat shock proteins (sHSPs/HSPBs) play important roles in maintaining proteostasis and protecting against proteotoxicity in MNDs. Understanding the role of HSPBs in MNDs may provide insights for developing therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Bruno Fauvet, Mathieu E. Rebeaud, Satyam Tiwari, Paolo De Los Rios, Pierre Goloubinoff
Summary: Life is a non-equilibrium phenomenon, where proteins fold and structure according to thermodynamic principles. Cells have evolved molecular chaperones to counteract protein misfolding and maintain structural stability.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Huafeng Xu
Summary: Recent experimental studies have shown that ATP-driven molecular chaperones can stabilize protein substrates in their native structures out of thermal equilibrium. This article proposes a unifying principle based on available evidence, which explains the conversion of chemical energy from ATP hydrolysis to the conformational free energy associated with protein folding and activation.
Article
Biochemistry & Molecular Biology
Burak Gulen, Amanda Casey, Kim Orth
Summary: Small GTPases play crucial roles in cellular pathways and are targeted by pathogens during infection. AMPylation, a common post-translational modification, is utilized by pathogens to hijack GTPase signaling. Understanding the AMPylation of small GTPases by pathogens contributes to the understanding of cellular infection mechanisms.
Article
Cell Biology
Zoe A. Feder, Asif Ali, Abhyudai Singh, Joanna Krakowiak, Xu Zheng, Vytas P. Bindokas, Donald Wolfgeher, Stephen J. Kron, David Pincus
Summary: The localization of J-protein Sis1, a cofactor for Hsp70, has been found to control HSR activation in yeast by forming an interconnected network with other proteostasis factors, directing Hsp70 activity away from Hsf1 in the nucleoplasm and allowing Hsf1 to induce the HSR.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Microbiology
Tilman Schirmer, Tjaart A. P. de Beer, Stefanie Tamegger, Alexander Harms, Nikolaus Dietz, David M. Dranow, Thomas E. Edwards, Peter J. Myler, Isabelle Phan, Christoph Dehio
Summary: This study elucidates the expansion and diversification of FIC domains in the Bartonella Bep repertoire using X-ray crystallography, structural modeling, and phylogenetic analysis. The findings reveal remarkable functional plasticity of Beps primarily due to structural changes in the substrate pocket and the target dock. These insights may guide future structure-function analyses of these highly versatile FIC domains.
Article
Cell Biology
Ernesto Llamas, Salvador Torres-Montilla, Hyun Ju Lee, Maria Victoria Barja, Elena Schlimgen, Nick Dunken, Prerana Wagle, Wolfgang Werr, Alga Zuccaro, Manuel Rodriguez-Concepcion, David Vilchez
Summary: Research has shown that root stem cells have the ability to resist protein aggregation, exhibiting enhanced protein stability and unique molecular chaperone expression. Additionally, high levels of TRiC/CCT complex activity in stem cells are crucial for maintenance and suppression of protein aggregation.
Article
Multidisciplinary Sciences
Marie Corteggiani, Nadege Bossuet-Greif, Jean-Philippe Nougayrede, Deborah Byrne, Marianne Ilbert, Sebastien Dementin, Marie-Therese Giudici-Orticoni, Vincent Mejean, Eric Oswald, Olivier Genest
Summary: Chaperone proteins, such as Hsp90, play a critical role in maintaining protein homeostasis in all living cells. Recent studies have shown that bacterial Hsp90 is essential for the survival of bacteria under stress conditions and is involved in the virulence of pathogenic bacteria. In this study, the researchers used site-directed mutagenesis to disrupt the binding between Hsp90 and the chaperone protein DnaK, and found that this collaboration is crucial for the folding of client proteins in bacteria. They also demonstrated that this collaboration between Hsp90 and DnaK in bacteria has evolved to form a more complex collaboration between Hsp70 and Hsp90 in eukaryotes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, General & Internal
Katharina Worzner, Daniel J. Sheward, Signe Tandrup Schmidt, Leo Hanke, Julie Zimmermann, Gerald McInerney, Gunilla B. Karlsson Hedestam, Ben Murrell, Dennis Christensen, Gabriel Kristian Pedersen
Summary: The study evaluated three different adjuvant systems combined with the SARS-CoV2 spike protein and found that they significantly enhanced antibody responses and neutralizing antibody titers. The oil-in-water emulsion system provided the most rapid response, with all adjuvanted groups developing neutralizing antibodies after a single dose. The specific CD4 T cell responses also varied depending on the adjuvant used.
Article
Multidisciplinary Sciences
Inga Szurgot, Leo Hanke, Daniel J. Sheward, Laura Perez Vidakovics, Ben Murrell, Gerald M. McInerney, Peter Liljestrom
Summary: The study compared the immunogenicity of two alphavirus-based DNA-launched self-replicating (DREP) vaccine candidates encoding different forms of the SARS-CoV-2 spike protein. It was found that the unmodified spike vaccine was more effective in inducing high levels of neutralizing antibodies in mice. Additionally, both vaccine candidates were able to prime immune responses against SARS-CoV-2 and could be enhanced with a heterologous spike protein immunization.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, General & Internal
X. Castro Dopico, S. Muschiol, M. Christian, L. Hanke, D. J. Sheward, N. F. Grinberg, J. Rorbach, G. Bogdanovic, G. M. Mcinerney, T. Allander, C. Wallace, B. Murrell, J. Albert, G. B. Karlsson Hedestam
Summary: Before the mass vaccination started, a study in Stockholm revealed that approximately 15% of individuals surveyed by December 13, 2020 tested positive, increasing to 19% by the end of February 2021. Notably, 96% of seropositive healthy donors developed neutralizing antibody responses comparable to those seen in clinical trials of SARS-CoV-2 mRNA vaccines, indicating a competent B-cell response from mild infections.
JOURNAL OF INTERNAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Bhaskar K. Chatterjee, Matthias C. Truttmann
Summary: AMPylation is the covalent attachment of an AMP moiety to target proteins using ATP, catalysed by AMP transferases. It plays a critical role in cell signalling in both bacteria and metazoans, with different types of AMPylases identified in each. The review compares bacterial and metazoan Fic and non-Fic AMPylases and summarizes recent advancements in the field.
Article
Biochemistry & Molecular Biology
Nicholas McCaul, Corey M. Porter, Anouk Becker, Chih-Hang Anthony Tang, Charlotte Wijne, Bhaskar Chatterjee, Djenet Bousbaine, Angelina Bilate, Chih-Chi Andrew Hu, Hidde Ploegh, Matthias C. Truttmann
Summary: FIC domain-containing AMP transferases play a crucial role in protein modification, with mFICD deficiency affecting protein synthesis and secretion in mice without affecting the unfolded protein response. Additionally, old mFICD-/- mice exhibit stronger nonspatial short-term learning compared to wild-type controls.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Geriatrics & Gerontology
Nicholas D. Urban, Joseph P. Cavataio, Yasmeen Berry, Brandon Vang, Anirudh Maddali, Richard J. Sukpraphrute, Santiago Schnell, Matthias C. Truttmann
Summary: The nematode Caenorhabditis elegans is widely used for studying various biological processes, but differences in experimental conditions and variations in chemical treatments or geographic locations can significantly influence the lifespan of N2 worms, leading to unreliable inter-laboratory comparisons. Standardized experimental protocols and improved reporting standards are needed to increase the reliability and reproducibility of lifespan studies in C. elegans.
EXPERIMENTAL GERONTOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Ainhoa Moliner-Morro, Gerald M. McInerney, Leo Hanke
Summary: This article discusses the importance of antibodies as natural antivirals and their role in virology research. It highlights the potential of camelid-derived nanobodies as a replacement for full-sized antibodies and their versatility in various applications.
JOURNAL OF GENERAL VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Leo Hanke, Daniel J. Sheward, Alec Pankow, Laura Perez Vidakovics, Vivien Karl, Changil Kim, Egon Urgard, Natalie L. Smith, Juan Astorga-Wells, Simon Ekstrom, Jonathan M. Coquet, Gerald M. McInerney, Ben Murrell
Summary: This study combines various techniques to identify and characterize nanobodies that neutralize SARS-CoV-2. The researchers found potent nanobodies that target specific regions of the virus, including two exceptionally potent ones. These nanobodies show the ability to neutralize different viral variants and even a related coronavirus.
Article
Neurosciences
Mirella A. Hernandez-Lima, Margaret Champion, Zachary Mattiola, Matthias C. Truttmann
Summary: In this study, the researchers investigated how the activity of the AMPylase FIC-1 affects physiological processes in Caenorhabditis elegans. They found that over-expression of FIC-1(E274G) impairs development, fertility, and stress resilience in C. elegans. The study also revealed that FIC-1(E274G) over-expression inhibits pathogen avoidance behavior by suppressing production of specific ligands in sensory neurons.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biotechnology & Applied Microbiology
Govind Gupta, Bejan Hamawandi, Daniel J. Sheward, Ben Murrell, Leo Hanke, Gerald McInerney, Magda Blosi, Anna L. Costa, Muhammet S. Toprak, Bengt Fadeel
Summary: Silver nanoparticles (Ag NPs) have been found to effectively inhibit SARS-CoV-2 infection, particularly the unmodified nanoparticles. This study also showed that the Ag NPs retained their antiviral properties even after pre-incubation with pulmonary surfactant. Additionally, the Ag NPs disrupted the secondary structure of the spike protein of SARS-CoV-2, while ionic control (AgNO3) and TiO2 nanoparticles did not have the same effect. Moreover, the Ag NPs were non-cytotoxic to human lung epithelial cells and nasal epithelial cells.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Taras Sych, Jan Schlegel, Hanna M. G. Barriga, Miina Ojansivu, Leo Hanke, Florian Weber, R. Beklem Bostancioglu, Kariem Ezzat, Herbert Stangl, Birgit Plochberger, Jurga Laurencikiene, Samir El Andaloussi, Daniel Fuerth, Molly M. Stevens, Erdinc Sezgin
Summary: Lipid nanoparticles, viruses, exosomes and liposomes can be characterized using fluorescence fluctuations analysis. A method called single-particle profiler is introduced to provide information on the content and biophysical properties of thousands of particles within the size range of 5-200 nm. The single-particle profiler is utilized to measure mRNA encapsulation efficiency of lipid nanoparticles, viral binding efficiencies of different nanobodies, and the biophysical heterogeneity of liposomes, lipoproteins, exosomes and viruses.
NATURE BIOTECHNOLOGY
(2023)
Article
Medicine, Research & Experimental
Jingdian Zhang, Camilla Koolmeister, Jinming Han, Roberta Filograna, Leo Hanke, Monika Adori, Daniel J. Sheward, Sina Teifel, Shreekara Gopalakrishna, Qiuya Shao, Yong Liu, Keying Zhu, Robert A. Harris, Gerald Mcinerney, Ben Murrell, Mike Aoun, Liselotte Baeckdahl, Rikard Holmdahl, Marcin Pekalski, Anna Wedell, Martin Engvall, Anna Wredenberg, Gunilla B. Karlsson Hedestam, Xaquin Castro Dopico, Joanna Rorbach
Summary: This study investigates the impact of pathogenic mutations in mitochondrial tRNA genes on the immune system. The results show that memory T and B cells have lower mutation burdens compared to their antigen-inexperienced naïve counterparts, and this reduction is less pronounced in myeloid lineages. The rapid dilution of the mutations in T and B cells can be induced by antigen receptor-triggered proliferation and is accelerated under metabolic stress conditions. In addition, the pathogenic mutations affect the metabolic remodeling and IFN-gamma production in CD8(+) T cells.
Article
Immunology
Xaquin Castro Dopico, Sandra Muschiol, Nastasiya F. Grinberg, Soo Aleman, Daniel J. Sheward, Leo Hanke, Marcus Ahl, Linnea Vikstrom, Mattias Forsell, Jonathan M. Coquet, Gerald McInerney, Joakim Dillner, Gordana Bogdanovic, Ben Murrell, Jan Albert, Chris Wallace, Gunilla B. Karlsson Hedestam
Summary: This study aimed to improve population-level measures of seropositivity for emerging pathogens. By using probabilistic learners to evaluate unknown samples, more accurate estimates of likelihood of seropositivity were provided.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2022)
Article
Cell Biology
Daniel J. Sheward, Marco Mandolesi, Egon Urgard, Changil Kim, Leo Hanke, Laura Perez Vidakovics, Alec Pankow, Natalie L. Smith, Xaquin Castro Dopico, Gerald M. McInerney, Jonathan M. Coquet, Gunilla B. Karlsson Hedestam, Ben Murrell
Summary: This study shows that immunization with a beta variant protein after Wu-Hu-1 spike vaccination can broaden neutralizing antibody responses to different VOCs. Plasma sampled after original virus immunization only partially protects mice from lethal challenge with a new variant, while plasma sampled after heterotypic variant boost provides complete protection against the disease.
CELL REPORTS MEDICINE
(2021)
Article
Cell Biology
Marco Mandolesi, Daniel J. Sheward, Leo Hanke, Junjie Ma, Pradeepa Pushparaj, Laura Perez Vidakovics, Changil Kim, Monika Adori, Klara Lenart, Karin Lore, Xaquin Castro Dopico, Jonathan M. Coquet, Gerald M. McInerney, Gunilla B. Karlsson Hedestam, Ben Murrell
Summary: The study demonstrates that protein immunization with adjuvanted SARS-CoV-2 spike trimers can induce potent neutralizing antibody responses in mice and rhesus macaques, with exceptionally high titers lasting at least 4 months.
CELL REPORTS MEDICINE
(2021)