Article
Microbiology
Mnar Ghrayeb, Shahar Hayet, Neta Lester-Zer, Yael Levi-Kalisman, Liraz Chai
Summary: Functional amyloid proteins are essential components in microbial biofilms, providing mechanical stability, mediating cell adhesion, and regulating biofilm development. The morphology of amyloid fibers, such as TasA, can vary based on environmental conditions and may serve different functional roles in biofilms, from mechanical support to acting as antibiotic agents.
Article
Microbiology
George Tetz, Victor Tetz
Summary: The study found that bacterial extracellular DNA can trigger Aβ protein aggregation, with the acceleration depending on the DNA concentration and bacterial strain. It suggests that bacterial DNA may play an important role in the pathogenesis of Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Carlos Molina-Santiago, Antonio de Vicente, Diego Romero
Summary: The extracellular matrix (ECM) is a complex megastructure produced by bacterial cells to form biofilms, with functions such as cell protection, modulation of cell-to-cell signaling, cell differentiation, and environmental sensing. ECM components like proteins, polysaccharides, and eDNA have specific functionalities and interact cooperatively to sustain ECM architecture. The diverse chemical composition and potential biotechnological applications of ECM components have attracted attention, from agriculture to water and food industries.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Macarena Siri, Melisa Herrera, Alejandro J. Moyano, M. Soledad Celej
Summary: Bacterial biofilms represent an alternative lifestyle for bacteria, and understanding the role of amyloid fibrils in these communities can provide insights into controlling biofilm formation. The study focused on FapC as a novel target to control Pseudomonas biofilms, and highlighted the impact of alginate on the morphology of FapC fibrils. This research emphasizes the importance of considering the complexity of the extracellular matrix in studying microbial functional amyloids.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Review
Biochemistry & Molecular Biology
Chu-Qiao Liang, Yan-Mei Li
Summary: The review highlights recent progress in peptide-based inhibitors, including amyloid sequence-derived inhibitors, designed peptides, and peptide mimics, towards pathological amyloid proteins and deposition. These peptides exhibit advanced inhibitory activities against fibrous aggregation as well as enhanced druggability, based on increased understanding of peptide design and precise amyloid structures.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Analytical
Laura Sola, Dario Brambilla, Alessandro Mussida, Roberto Consonni, Francesco Damin, Marina Cretich, Alessandro Gori, Marcella Chiari
Summary: A new polymeric coating was introduced to co-immobilize proteins and oriented peptides on the same substrate, facilitating the phenotype characterization of extracellular vesicles. Through NMR characterization and post polymerization modification, the strategy could reduce the number of analysis, save time, reagents, and costs.
ANALYTICA CHIMICA ACTA
(2021)
Article
Cell Biology
Meredith Whitehead, Syabira Yusoff, Sadia Ahmad, Lukas Schmidt, Manuel Mayr, Jillian Madine, David Middleton, Catherine M. Shanahan
Summary: Vascular amyloidosis, caused by the aggregation of peptide monomers into insoluble amyloid, is a common age-related pathology. This study found that extracellular vesicles (EVs) and HSPG2 in the extracellular matrix (ECM) play key roles in medin accumulation, contributing to the development of age-associated aortic medial amyloid (AMA).
Review
Engineering, Chemical
Yanxian Zhang, Yijing Tang, Dong Zhang, Yonglan Liu, Jian He, Yung Chang, Jie Zheng
Summary: The research focuses on the mechanism of amyloid cross-seeding between Aβ and hIAPP and its connection between AD and T2D, explores the role of structural compatibility and sequence similarity of amyloid proteins in cross-seeding, and proposes current challenges and future research directions in this less-studied field.
CHINESE JOURNAL OF CHEMICAL ENGINEERING
(2021)
Review
Biochemistry & Molecular Biology
Anna Sulatskaya, Anastasiia O. Kosolapova, Alexander G. Bobylev, Mikhail Belousov, Kirill S. Antonets, Maksim Sulatsky, Irina M. Kuznetsova, Konstantin K. Turoverov, Olesya Stepanenko, Anton A. Nizhnikov
Summary: Both amyloids and beta-barrel proteins have beta-sheet-rich structures, with the latter being able to form functional amyloids in vivo. These beta-barrel amyloid proteins can interact with each other and form toxic oligomers, potentially contributing to the development of amyloidoses. Rapidly growing discoveries suggest that the number and diversity of functions of amyloid-forming beta-barrel proteins are significantly greater than currently understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yang Gao, Stefan Wennmalm, Bengt Winblad, Sophia Schedin-Weiss, Lars O. Tjernberg
Summary: Through FRET imaging, Aβ42 oligomerization was successfully detected in primary neurons, showing that Aβ42 oligomerized in lysosomes/late endosomes in a concentration-dependent manner. These findings contribute to a better understanding of Aβ42 oligomerization in neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jofre Seira Curto, Maria Rosario Fernandez, Josep Cladera, Nuria Benseny-Cases, Natalia Sanchez de Groot
Summary: Homeostasis is crucial for cell function and disturbances in homeostasis can lead to health disorders. This study investigated how pH levels affect the aggregation of amyloid-beta-peptide (A beta) and the development of Alzheimer's disease. The results showed that the brain pH and different aggregated conformations play a role in the aggregation process. Furthermore, neutral pH and physiological salt concentrations were found to favor a slow aggregation with low cytotoxic effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Nan Yuan, Lianmeng Ye, Yan Sun, Hao Wu, Zhengpan Xiao, Wanmeng Fu, Zuqian Chen, Yechun Pei, Yi Min, Dayong Wang
Summary: The major pathological feature of Alzheimer's disease (AD) is the aggregation of amyloid beta peptide (A beta) in the brain. Inhibition of A beta(42) aggregation may prevent the advancement of AD. This study found that arginine dipeptide (RR) was the most effective at interfering with A beta(42) polymerization and reducing its toxicity, including cell death, reactive oxygen species (ROS) production, and apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Michael C. Wilson, Qin Lu, Kaitlin R. Nachtrieb, Jackson S. Fuller, Chloe M. Skogg, Elizabeth A. Yates, Matthew D. Thum, Christopher R. So
Summary: This study demonstrates the chemical aggregation of common hydrophilic proteins into an aqueous adhesive similar to natural adhesives. By using multiple chemical denaturants, rapid gelation and further curing in artificial seawater can be achieved. The adhesive strengths of this waterborne adhesive are comparable to bioinspired adhesives that use organic solvents and hydrophobic components. This approach enables the deployment of a bioinspired adhesive at practical scales in marine environments, with sustainable production and low-cost materials.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Chemistry, Physical
Debanjan Bagchi, Avijit Maity, Soumya Kanti De, Anjan Chakraborty
Summary: For the first time, this study reports the existence of different metastable intermediate states during the self-assembly process of phenylalanine in the presence of various metal ions. The metal ion-amino acid interactions lead to the initial formation of spherical aggregates, which then transform into other structures. These findings contribute to a better understanding of the role of metal ions in amino acid self-assembly.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Multidisciplinary Sciences
Tessa Sinnige, Georg Meisl, Thomas C. T. Michaels, Michele Vendruscolo, Tuomas P. J. Knowles, Richard Morimoto
Summary: Protein aggregation in a Caenorhabditis elegans model is controlled by independent, stochastic nucleation events in individual cells, highlighting the importance of biophysical principles in governing the overall progression of polyQ aggregation in a living animal.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Engineering, Manufacturing
Pernille Thestrup Rikvold, Karina Kambourakis Johnsen, Dirk Leonhardt, Andreas Mollebjerg, Signe Maria Nielsen, Lea Benedicte Skov Hansen, Rikke Louise Meyer, Sebastian Schlafer
Summary: This study designed and validated an additively manufactured intraoral device for the collection of dental biofilms. Additive manufacturing reduced production time and cost, ensuring accurate fit and easy handling of biofilm carriers. The biofilms exhibited typical architecture and composition, with moderate variation in growth.
3D PRINTING AND ADDITIVE MANUFACTURING
(2023)
Article
Immunology
Katharina Opstrup, Gunna Christiansen, Svend Birkelund
Summary: Klebsiella pneumoniae is an opportunistic pathogen that causes bacteremia. Ceftazidime and meropenem induce morphological changes in bacteria. The study analyzed the resistance and susceptibility of Klebsiella spp. Bacteremia isolates to these antibiotics in different serum conditions. The findings revealed that serum and beta-lactam antibiotics can induce morphological changes in bacteria, with some strains showing increased sensitivity to beta-lactam antibiotics.
MICROBES AND INFECTION
(2023)
Article
Immunology
Katharina Opstrup, Tue B. Bennike, Gunna Christiansen, Svend Birkelund
Summary: Klebsiella pneumoniae, an opportunistic gram-negative pathogen, was analyzed for serum susceptibility in normal human serum (NHS). The study found that the activation of complement cascades is crucial for killing bacteria in plasma. The concentration-dependent functionality of the alternative pathway (AP) was observed in the killing of the isolates.
MICROBES AND INFECTION
(2023)
Article
Biochemistry & Molecular Biology
Saeid Hadi Ali Janvand, Lucy Kate Ladefoged, Asta Zubriene, Andrius Sakalauskas, Gunna Christiansen, Virginija Dudutiene, Birgit Schiott, Daumantas Matulis, Vytautas Smirnovas, Daniel E. Otzen
Summary: Fluorinated sulfonamide compounds can inhibit the formation of amyloid fibrils, potentially providing therapeutic effects against amyloid-related disorders such as Parkinson's, Alzheimer's, and type 2 diabetes, possibly by maintaining insulin in its native monomeric state.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Multidisciplinary Sciences
Marie-Lise Jobin, Sana Siddig, Zsombor Koszegi, Yann Lanoiselee, Vladimir Khayenko, Titiwat Sungkaworn, Christian Werner, Kerstin Seier, Christin Misigaiski, Giovanna Mantovani, Markus Sauer, Hans M. Maric, Davide Calebiro
Summary: GABA(B) receptors are precisely located and regulated by dynamic interactions with Filamin A, which is a cytoskeletal protein. This study provides evidence that the spatial organization and diffusion of GABA(B) receptors on the plasma membrane are governed by Filamin A, and these interactions modulate the kinetics of G alpha(i) protein activation in response to GABA stimulation.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Pascal Dominic Rem, Vita Sereikaite, Diego Fernandez-Fernandez, Sebastian Reinartz, Daniel Ulrich, Thorsten Fritzius, Luca Trovo, Salome Roux, Ziyang Chen, Philippe Rondard, Jean-Philippe Pin, Jochen Schwenk, Bernd Fakler, Martin Gassmann, Tania Rinaldi Barkat, Kristian Stromgaard, Bernhard Bettler
Summary: Amyloid-beta precursor protein (APP) regulates neuronal activity through the release of secreted APP (sAPP) acting at cell surface receptors. A 17 amino acid peptide (APP17) derived from APP binds to the extracellular sushi domain 1 (SD1) of GABA(B) receptors (GBRs). However, APP17 does not influence GBR activity in heterologous cells, indicating that sAPP exerts its neuronal effects through receptors other than GBRs.
Article
Engineering, Chemical
Andreas Mollebjerg, Agata Zarebska, Henrik Bangso Nielsen, Lea Benedicte Skov Hansen, Sebastian R. Sorensen, Bozena Seredynska-Sobecka, Loreen O. Villacorte, Klaus Gori, Lorena Gonzalez Palmen, Rikke Louise Meyer
Summary: Biofouling is a widespread problem in industrial systems, such as reverse osmosis (RO) desalination units, where biofilms impede water flow. Enzymes have shown promise as non-damaging and environmentally friendly cleaning agents for biofilms, but identifying effective enzymes is challenging. To overcome this, a flexible screening platform was developed to directly evaluate enzyme treatment on fouled RO membranes. This platform identified enzymes, including proteases, lipases, DNase, cellulolytic enzymes, and pectin-degrading enzymes, that effectively degraded biofilms on RO membranes. The most effective enzyme formulations outperformed chemical cleaning agents, removing 45% of the biofilm compared to 0%-19% for chemicals (p <= 0.001), highlighting the potential of enzymes as replacements or complements to chemical cleaning. The screening platform proved to be a powerful tool for studying and combating biofilms in various applications.
Article
Chemistry, Medicinal
Christian R. O. Bartling, Flora Alexopoulou, Sarah Kuschert, Yanni K. -Y. Chin, Xinying Jia, Vita Sereikaite, Dennis Ozcelik, Thomas M. Jensen, Palash Jain, Mads M. Nygaard, Kasper Harpsoe, David E. Gloriam, Mehdi Mobli, Kristian Stromgaard
Summary: Peptides targeting disease-relevant protein-protein interactions have limitations in terms of metabolic stability and membrane permeability. Peptide cyclization, particularly hydrocarbon stapling, offers a valuable approach to develop metabolically stable and cell-permeable cyclic leads with improved affinity and stability. In this study, a comprehensive examination of cyclization strategies led to the identification of cyclic APP dodecamer peptides that target the phosphotyrosine binding domain of Mint2 with significantly improved properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Thorbjorn Sonderby, Nikolaos N. Louros, Ladan Khodaparast, Laleh Khodaparast, Daniel J. Madsen, William P. Olsen, Nele Moonen, Madhu Nagaraj, Vita Sereikaite, Kristian Stromgaard, Frederic Rousseau, Joost Schymkowitz, Daniel E. Otzen
Summary: Functional bacterial amyloid provides structural stability in biofilm, which can be targeted for anti-biofilm therapeutics. Aggregation-modulating peptides can be used to disrupt the stability and morphology of amyloid proteins, such as CsgA and FapC, resulting in reduced biofilm formation in E. coli and P. aeruginosa. This study demonstrates the potential of selective amyloid targeting in combating bacterial biofilm.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Thamara Nishida Xavier da Silva, Clemens Schulte, Ariane Nunes Alves, Hans Michael Maric, Jose Pedro Friedmann Angeli
Summary: Ferroptosis is a form of cell death characterized by phospholipid peroxidation. The inhibition of Ferroptosis suppressor protein 1 (FSP1) has been shown to sensitize cancer cells to ferroptosis. In this study, the species-specific inhibition of a first-generation FSP1 inhibitor, iFSP1, on the human isoform is explored to gain insights into its mechanism of action.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
Jan H. Voss, Max Cruesemann, Christian R. O. Bartling, Stefan Kehraus, Asuka Inoue, Gabriele M. Koenig, Kristian Stromgaard, Christa E. Mueller
Summary: This study investigated the inhibitory effects of macrocyclic depsipeptides YM-254890 and FR900359 on Gaq/11 proteins and observed significant differences in dissociation kinetics between these compounds and their hydrogenated, tritium-labeled derivatives. Results showed that small structural modifications had a major impact on the residence time of the macrocyclic depsipeptides. FR exhibited pseudo-irreversible binding, while YM had a faster dissociation rate. The isopropyl anchor in FR and some derivatives was found to be essential for slow dissociation. These findings provide a basis for future drug design strategies to modulate residence times of macrocyclic Gq protein inhibitors, which play a crucial role in therapeutic outcomes.
Article
Neurosciences
Shawna M. Henry, Sabrina A. Kistler, Gavin D. Lagani, Christian R. O. Bartling, Dennis Ozcelik, Vita Sereikaite, Kristian Stromgaard, Uwe Beffert, Angela Ho
Summary: Mutations in Mint1 protein can modulate its interaction with APP and affect the generation and secretion of Aβ peptides. Enhancing or reducing the binding affinity between Mint1 and APP can regulate the production and release of Aβ peptides, providing a potential therapeutic target for Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Laura Lind Throne Degn, Ditte Bech, Gunna Christiansen, Svend Birkelund
Summary: Chlamydia trachomatis is the major cause of sexually transmitted diseases and understanding the role of antibodies in its infection process is important for vaccine development. By investigating the specificity and binding characteristics of two monoclonal antibodies against the major outer membrane protein (MOMP) of C. trachomatis, this study provides insights into the protective contribution of antibodies and their limitations in reducing infectivity.
MOLECULAR IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Flora Alexopoulou, Nina Buch-Manson, Soren ljungberg Pedersen, Niels Vrang, Lisbeth Nielsen Fink, Kristian Stromgaard
Summary: GDF15 peptide fragments can serve as valuable tools for the development of peptide therapeutics for the treatment of cachexia and other wasting disorders.
Article
Cell Biology
Dominique C. S. Evans, Amanda B. Khamas, Lisbeth Marcussen, Kristian S. Rasmussen, Janne K. Klitgaard, Birgitte H. Kallipolitis, Janni Nielsen, Daniel E. Otzen, Mark C. Leake, Rikke L. Meyer
Summary: This study demonstrates the feasibility of using the monomeric superfolder GFP (msfGFP) exported from Staphylococcus aureus as a fluorescent reporter. By fusing msfGFP to potential signal peptides, the secretion of proteins from S. aureus was successfully studied. Our findings suggest that msfGFP is an ideal fluorescent reporter to consider when studying proteins secreted by the Sec pathway in S. aureus.
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)