Article
Biochemistry & Molecular Biology
Qize Xuan, Jiaxin He, Wenxue Zhang, Wei Zhang, Qi Zhang, Yao Zhou, Anqi Wei, Hao Wang, Hui Li, Chao Chen, Ping Wang
Summary: This study successfully prepared three different morphological and structural phenol-soluble modulin alpha 3 (PSM alpha 3) assemblies using the strategy of salt-inducing assembly polymorphism. It was found that amyloid fibrillation was essential for enhancing the cytotoxicity of PSM alpha 3, and the size and structure of PSM alpha 3 fibrils played a crucial role in cytotoxicity. The cytotoxicity was achieved through a membrane-disrupting mechanism, with different fibril types causing membrane thinning or perforation.
Review
Chemistry, Multidisciplinary
Dmitry Kurouski
Summary: The aggregation of misfolded proteins in amyloidogenic diseases is influenced by lipids, which can alter the aggregation rate, secondary structure, and morphology of protein oligomers and fibrils. Lipids also affect the toxicity of amyloid oligomers and fibrils. Furthermore, pathological changes in lipid composition may trigger protein aggregation and lead to the formation of highly toxic oligomers and fibrils. Polyunsaturated fatty acids have a significant impact on the aggregation properties of amyloidogenic proteins.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Shean-Jaw Chiou, Huey-Jiun Ko, Chi-Ching Hwang, Yi-Ren Hong
Summary: Beta2-microglobulin (B2M) plays a crucial role in both immune response and antimicrobial activity, functioning primarily in innate defense. B2M acts as an antimicrobial peptide under acidic conditions, disrupting a wide range of microbes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Aruna K. Mora, Sushant Murudkar, Neelam Shivran, Soumyaditya Mula, Subrata Chattopadhyay, Sukhendu Nath
Summary: Protein oligomers, formed under physiological stress, are neurotoxic and linked to neurological diseases. Early detection is crucial, and a new NIR-emitting fluorescent probe has been developed for this purpose. The probe not only detects matured fibrils but also probes oligomer formation, showing potential for in vivo imaging.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Biochemistry & Molecular Biology
Parveen Salahuddin, Munazza Tamkeen Fatima, Vladimir N. Uversky, Rizwan Hasan Khan, Zeyaul Islam, Mohammad Furkan
Summary: Neurodegenerative diseases are characterized by the abnormal loss of neurons, with common pathogenic mechanisms involving misfolding and aggregation of proteins. Accumulating evidence suggests that amyloid oligomers, not fibrils, are the most toxic species causing AD and PD.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Addison Frese, Cody Goode, Kiryl Zhaliazka, Aidan P. Holman, Tianyi Dou, Dmitry Kurouski
Summary: The aggregation of misfolded proteins is the fundamental molecular cause of severe pathologies such as Alzheimer's and Parkinson's diseases. Lipids are found to play a vital role in this process. In this study, the researchers investigated the impact of the length and saturation of fatty acids in phosphatidylserine (PS) on lysozyme aggregation. The results showed that both factors influenced the aggregation rate of insulin. The presence of double bonds in fatty acids accelerated the rate of insulin aggregation relative to PS with fully saturated fatty acids.
Article
Biochemistry & Molecular Biology
Carlton Ranjith Wilson Alphonse, Rajaretinam Rajesh Kannan, Nagasundaram Nagarajan
Summary: Amyloid beta-protein (ABP) is the major cause of Alzheimer's disease. Family mutations in A beta increase aggregation, particularly in the nonapeptide segment. Molecular dynamics simulation shows that the interaction between PITRM1 and A beta nonapeptide segment is similar, except for the Arctic mutant. This research provides insights into eliminating different types of A beta family mutants in neurodegenerative cells.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Xiuhua Yin, Hong Zhou, Mengling Zhang, Juan Su, Xiao Wang, Sijie Li, Zaixing Yang, Zhenhui Kang, Ruhong Zhou
Summary: This study discovered an ultra-small nanodot, C3N, that inhibits the aggregation of A beta peptides and improves behavioral deficits in an AD mouse model. C3N nanodots not only reduce the levels of A beta peptides but also protect neurons and synapses.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Wujoon Cha, Chaejeong Heo, Sanghyub Lee, Seok Joon Yun, Byeong Wook Cho, Taewoo Ha, Young Hee Lee
Summary: Charge transfer during the fibrillization of A ss proteins was investigated using Raman spectroscopy. The study revealed that small A ss monomers withdraw electrons, while fibrils donate electrons to graphene and molybdenum disulfide. Oligomers undergo transient charge states near the neutrality point.
Article
Biochemistry & Molecular Biology
Fatima Kamal Zaidi, Rajiv Bhat
Summary: This study investigates the influence of curcumin and EGCG on the amyloid fibril formation of human lysozyme (HuL) and explores the mechanisms of their action. Curcumin inhibits HuL fibrillation by interacting with prefibrillar and fibrillar intermediates, while also disaggregating preformed fibrils. On the other hand, EGCG suppresses fibrillation but modulates the pathway towards large, β-sheet rich amyloid fibril-like aggregates and modifies preformed fibrils. Despite forming large agglomerates, both curcumin and EGCG reduce the surface hydrophobicity and cytotoxicity of HuL, possibly due to the dense and highly clustered nature of the aggregates.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Multidisciplinary Sciences
Juliana Rey, Maike Breiden, Vanda Lux, Anika Bluemke, Maike Steindel, Kamilla Ripkens, Bastian Moellers, Kenny Bravo Rodriguez, Prisca Boisguerin, Rudolf Volkmer, Joel Mieres-Perez, Tim Clausen, Elsa Sanchez-Garcia, Michael Ehrmann
Summary: This study reports a novel and reversible mechanism of protease activation, where an inactive protease serves as the activator. This mechanism involves the formation of an allosteric complex between HTRA1 and calpain 2, and exhibits activity only towards specific conformations of substrates. These findings have important implications for understanding protein quality control and potential side effects of drug modulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Pranita Rananaware, Parimal Pandit, Seekha Naik, Monalisa Mishra, Rangappa S. Keri, Varsha P. Brahmkhatri
Summary: Quercetin, a plant polyphenol with antioxidant and anti-inflammatory activity, has been conjugated with polyvinylpyrrolidone and gold nanoparticles to form nanorods. These conjugates show enhanced drug release and inhibit amyloid aggregation in lysozyme, making them potential therapeutic agents for neurological diseases like Alzheimer's and Parkinson's.
Article
Chemistry, Physical
Mikhail Matveyenka, Stanislav Rizevsky, Dmitry Kurouski
Summary: Lipid bilayers play a crucial role in the pathological assembly of amyloidogenic proteins and peptides, and unsaturated phospholipids catalyze the formation of more toxic amyloid aggregates.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Physical
Debasis Saha, Biman Jana
Summary: This study investigates the intermediates in the fibril formation pathway of A beta(13-42) oligomers and identifies their stable conformations and structural features. Residues 30-36 are found to play a crucial role in fibril formation.
Article
Biochemistry & Molecular Biology
Kiryl Zhaliazka, Mikhail Matveyenka, Dmitry Kurouski
Summary: Abrupt aggregation of amyloid beta(1-42) (Aβ) peptide is a hallmark of Alzheimer's disease (AD), and lipids have been found to uniquely alter the rate and structure of Aβ(1-42) aggregation. In this study, the effect of phosphatidylcholine (PC), cardiolipin (CL), and cholesterol (Chol) on Aβ(1-42) aggregation was investigated. The results showed that these lipids significantly accelerated the rate of fibril formation and modified the secondary structure of Aβ(1-42) aggregates.
Article
Biochemistry & Molecular Biology
Giulia Mazzini, Stefano Ricagno, Serena Caminito, Paola Rognoni, Paolo Milani, Mario Nuvolone, Marco Basset, Andrea Foli, Rosaria Russo, Giampaolo Merlini, Giovanni Palladini, Francesca Lavatelli
Summary: AL amyloidosis is characterized by the deposition of immunoglobulin light chains in target organs, with LC fragments consistently present in deposits. The fragmentation sites of LCs were found to be consistent across multiple organs but with some organ-specific positions, possibly due to a complex of proteases. Cleavage sites are concentrated in 'proteolysis-prone' regions, common to all tissues. Several proteolytic sites are not accessible on native dimers, while they are compatible with fibrils. This suggests that the heterogeneous ensemble of LC fragments originates in tissues and is consistent with digestion of preformed fibrils.
Article
Biochemistry & Molecular Biology
Giacomo Quilici, Andrea Berardi, Chantal Fabris, Michela Ghitti, Marco Punta, Louise J. Gourlay, Martino Bolognesi, Giovanna Musco
Summary: The SYLF domain of the BPSL1445 protein, a seroreactive antigen and diagnostic marker of Burkholderia pseudomallei, shows a beta-barrel core structure with flexible loops and helices. The study reveals weak interactions with phosphoinositides, supporting lipid binding abilities in prokaryotes and suggesting a common ancestry with bacterial EipA domains.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rosaria Russo, Margherita Romeo, Tim Schulte, Martina Maritan, Luca Oberti, Maria Monica Barzago, Alberto Barbiroli, Carlo Pappone, Luigi Anastasia, Giovanni Palladini, Luisa Diomede, Stefano Ricagno
Summary: This study demonstrates the specific binding of Cu2+ to the variable domain of amyloidogenic H7 with a sub-micromolar affinity using microscale thermophoresis, isothermal calorimetry and thermal melting. The binding of copper ions is just one of the several biochemical traits contributing to light chain amyloidosis soluble toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Flavio Di Pisa, Stefano De Benedetti, Enrico Mario Alessandro Fassi, Mauro Bombaci, Renata Grifantini, Angelo Musico, Roberto Frigerio, Angela Pontillo, Cinzia Rigo, Sandra Abelli, Romualdo Grande, Nadia Zanchetta, Davide Mileto, Alessandro Mancon, Alberto Rizzo, Alessandro Gori, Marina Cretich, Giorgio Colombo, Martino Bolognesi, Louise Jane Gourlay
Summary: Chagas disease is a vector-borne parasitic disease caused by the protozoan parasite Trypanosoma cruzi. It is affecting millions of people worldwide and is emerging in non-endemic regions due to climate change and increased immigration. This study focuses on developing new serodiagnostic molecules for early screening of the disease. A recombinant surface membrane antigen from T. cruzi was produced and its ability to detect plasma antibodies from infected patients was confirmed. The crystal structure of the antigen was also determined to guide the design of epitopes for CD diagnosis.
Review
Biochemistry & Molecular Biology
Marco Nardini, Alessandra Pesce, Martino Bolognesi
Summary: Truncated hemoglobins (trHbs) are a subclass of the globin family found in various organisms, including human pathogens. They have specific structural features and support different functions, such as detoxification, respiration, and oxygen sensing/storage.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Article
Multidisciplinary Sciences
Emanuele Scalone, Luca Broggini, Cristina Visentin, Davide Erba, Fran Bacic Toplek, Kaliroi Peqini, Sara Pellegrino, Stefano Ricagno, Cristina Paissoni, Carlo Camilloni
Summary: Understanding the mechanisms of protein aggregation is crucial for treating over 50 incurable diseases. A new hybrid structure model presented in this study effectively captures the essential structural and kinetic aspects of protein aggregation through molecular dynamics simulations. This model can help observe the formation of primary nuclei and the growth of fibrils, providing a structural basis for designing drugs targeting amyloidogenic diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Virology
Rafaela Milan Bonotto, Francesco Boni, Mario Milani, Antonio Chaves-Sanjuan, Silvia Franze, Francesca Selmin, Tommaso Felicetti, Martino Bolognesi, Soultana Konstantinidou, Monica Poggianella, Chantal L. Marquez, Federica Dattola, Monica Zoppe, Giuseppe Manfroni, Eloise Mastrangelo, Alessandro Marcello
Summary: Pyridobenzothiazolone derivatives are a promising class of antiviral compounds with broad-spectrum activity. The HeE1-17Y derivative has been shown to be potent against flaviviruses and West Nile virus. It interacts directly with viral particles, compromising their infectivity. This compound alters the viral membrane and exhibits virucidal activity.
Article
Biotechnology & Applied Microbiology
Ferdinando M. Milazzo, Antonio Chaves-Sanjuan, Olga Minenkova, Daniela Santapaola, Anna M. Anastasi, Gianfranco Battistuzzi, Caterina Chiapparino, Antonio Rosi, Emilio Merlo Pich, Claudio Albertoni, Emanuele Marra, Laura Luberto, Cecile Viollet, Luigi G. Spagnoli, Anna Riccio, Antonio Rossi, Gabriella Santoro, Federico Ballabio, Cristina Paissoni, Carlo Camilloni, Martino Bolognesi, Rita De Santis
Summary: A human single-chain antibody called scFv76 can neutralize different variants of SARS-CoV-2 and demonstrate therapeutic efficacy in a mouse model of COVID-19, reducing lung inflammation and endothelial damage.
Article
Biochemistry & Molecular Biology
Michela Bollati, Kaliroi Peqini, Luigi Barone, Carmina Natale, Marten Beeg, Marco Gobbi, Luisa Diomede, Michelangelo Trucchi, Matteo de Rosa, Sara Pellegrino
Summary: Gelsolin amyloidosis is a disease characterized by abnormal deposition of gelsolin protein in tissues, for which there is currently no cure. Researchers have designed and synthesized three peptidomimetics that effectively inhibit the aggregation of amyloidogenic peptides and have demonstrated their efficacy in vivo. These findings provide a new pharmacological strategy against gelsolin amyloidosis and suggest potential applications in other amyloidogenic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Tim Schulte, Antonio Chaves-Sanjuan, Giulia Mazzini, Valentina Speranzini, Francesca Lavatelli, Filippo Ferri, Carlo Palizzotto, Maria Mazza, Paolo Milani, Mario Nuvolone, Anne-Cathrine Vogt, Giovanni Palladini, Giampaolo Merlini, Martino Bolognesi, Silvia Ferro, Eric Zini, Stefano Ricagno
Summary: AA amyloidosis is a systemic disease characterized by the deposition of misfolded serum amyloid A protein (SAA) in multiple organs. The cryo-EM structure of AA amyloid from a cat with renal failure reveals a feline-specific sequence insert in the fibril core, which is highly similar to AA amyloid from cheetah with reported prion-like transmission.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Javier Garcia-Pardo, Andrea Bartolome-Nafria, Antonio Chaves-Sanjuan, Marcos Gil-Garcia, Cristina Visentin, Martino Bolognesi, Stefano Ricagno, Salvador Ventura
Summary: The study reports the cryo-electron microscopy structure of hnRNPDL-2 fibrils, revealing its stable, non-toxic, and nucleic acid-binding properties. The structure provides insights into the mechanism of hnRNPDL-2 fibrillation and its association with LGMD D3. Additionally, the study highlights how alternative splicing controls the assembly of different hnRNPDL isoforms, generating functional diversity.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Ida Freda, Cecile Exertier, Anna Barile, Antonio Chaves-Sanjuan, Mirella Vivoli Vega, Michail N. Isupov, Nicholas J. Harmer, Elena Gugole, Paolo Swuec, Martino Bolognesi, Anita Scipioni, Carmelinda Savino, Martino Luigi Di Salvo, Roberto Contestabile, Beatrice Vallone, Angela Tramonti, Linda Celeste Montemiglio
Summary: Specificity in protein-DNA recognition is determined by the structural and chemical features of the targeted DNA molecule. Using cryo-EM and crystallography, we elucidated the interactions driving the DNA recognition and binding by PdxR, a bacterial transcription factor. Our findings revealed the importance of electrostatic interactions and DNA bending in the allosteric regulation of DNA binding by PdxR. This study provides detailed insights into the structure and dynamics of the PdxR-DNA complex and the regulatory mechanisms of the MocR family of transcription factors.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Kevin P. Guay, Roberta Ibba, J. L. Kiappes, Snezana Vasiljevic, Francesco Boni, Maria De Benedictis, Ilaria Zeni, James D. Le Cornu, Mario Hensen, Anu V. Chandran, Anastassia L. Kantsadi, Alessandro T. Caputo, Juan I. Blanco Capurro, Yusupha Bayo, Johan C. Hill, Kieran Hudson, Andrea Lia, Juliane Brun, Stephen G. Withers, Marcelo Marti, Emiliano Biasini, Angelo Santino, Matteo De Rosa, Mario Milani, Carlos P. Modenutti, Daniel N. Hebert, Nicole Zitzmann, Pietro Roversi
Summary: This study discovered that the small molecule compound 5M-8OH-Q has inhibitory effects on UGGT and holds potential applications in broad-spectrum antiviral drugs and rescue therapy for glycoprotein mutation diseases. Additionally, the binding mechanism of 5M-8OH-Q is distinct from other GT24 family glycosyltransferases.
Article
Multidisciplinary Sciences
Mauricio Aguilar Rangel, Alice Bedwell, Elisa Costanzi, Ross J. Taylor, Rosaria Russo, Goncalo J. L. Bernardes, Stefano Ricagno, Judith Frydman, Michele Vendruscolo, Pietro Sormanni
Summary: The method describes a fragment-based approach to design antibody binding loops and graft them onto antibody scaffolds, providing a starting point for rapidly generating lead antibodies binding to preselected epitopes without the need for a high-resolution input antigen structure.