Article
Biology
Eugene Serebryany, Sourav Chowdhury, Christopher N. Woods, David C. Thorn, Nicki E. Watson, Arthur A. McClelland, Rachel E. Klevit, Eugene Shakhnovich
Summary: Cataract, a protein aggregation disorder, is a common cause of vision loss worldwide. Researchers have discovered that myo-inositol, an abundant lens metabolite, can suppress the aggregation of lens crystallins, suggesting it as a potential strategy to prevent or delay age-onset cataracts.
Review
Biochemistry & Molecular Biology
Kevin Reinle, Axel Mogk, Bernd Bukau
Summary: The protein quality control system maintains protein homeostasis through substrate degradation, refolding, and sequestration activities, in which small heat shock proteins play a crucial role and adapt to different tasks and stress conditions.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vera A. Borzova, Svetlana G. Roman, Anastasiya V. Pivovarova, Natalia A. Chebotareva
Summary: Intracellular proteins aggregation can be enhanced under stress. Heat-shock proteins (HSPs) and accumulation of osmolytes are cellular protective mechanisms. The antiaggregation activity of HSPB5 can be affected by crowding agents and osmolytes, and different additives can either improve or impair its activity against different protein targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Chemistry, Multidisciplinary
Evelyn Rose Kamski-Hennekam, Jinfeng Huang, Rashik Ahmed, Giuseppe Melacini
Summary: The ability of ATP to modulate protein solubility is critical in understanding proteinopathies like Parkinson's disease. ATP levels decline with age, which is the most significant risk factor for Parkinson's. This study shows that ATP affects multiple stages of alpha-synuclein aggregation, and the disruption of ATP's function may play a role in Parkinson's etiology.
Article
Biochemistry & Molecular Biology
Mantas Ziaunys, Andrius Sakalauskas, Tomas Sneideris, Vytautas Smirnovas
Summary: Protein aggregation into amyloid fibrils is associated with various disorders, but the mechanisms behind the conversion of non-harmful proteins into such aggregates are not fully understood. Recent studies suggest that multiple types of protein aggregates may co-exist in tissues of patients with amyloid-related disorders, potentially influencing each other.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Bhumika Pippal, Paramita Chaudhuri, Khushboo Rani, Jay Kant Yadav, Neha Jain
Summary: Altered protein folding leading to structured aggregates like amyloid fibrils is associated with neurodegenerative diseases. This study focuses on the modulation of alpha-synuclein amyloid assembly by a complex of bovine eye lens protein, alpha-crystallin. The results show that alpha-crystallin inhibits alpha-synuclein amyloid formation and drives it into soluble intermediates, suggesting its potential as a therapeutic target for neurodegenerative diseases.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Alexander G. Bobylev, Roman S. Fadeev, Liya G. Bobyleva, Margarita I. Kobyakova, Yuri M. Shlyapnikov, Daniil V. Popov, Ivan M. Vikhlyantsev
Summary: The study found that amyloid aggregates of smooth-muscle titin can impair cell adhesion and lead to cell death. The surface roughness may be a key factor contributing to the highly antiadhesive properties. The negative impact of amyloid aggregates on cell adhesion is likely intrinsic to other amyloid proteins with similar structure and properties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Mantas Ziaunys, Kamile Mikalauskaite, Andrius Sakalauskas, Vytautas Smirnovas
Summary: The aggregation of amyloidogenic proteins is related to various diseases, with limited treatment options currently available. The challenge in the discovery of potential anti-amyloid molecules lies in identifying the actual inhibitors from complex mixtures. This study successfully scavenged potential aggregation-inhibiting molecules from different compounds and effectively separated them from the aggregates.
BIOTECHNOLOGY JOURNAL
(2021)
Review
Cell Biology
Nicholas J. J. Geraghty, Sandeep Satapathy, Mark R. R. Wilson
Summary: The immune system is crucial for organism protection. Complement and ECs play important roles in maintaining protein homeostasis and controlling immune processes. They may interact with pathogens and immune responses, and influence the development of various diseases.
Review
Biochemistry & Molecular Biology
Kalliopi Ziaka, Jacqueline van der Spuy
Summary: This review explores the role of Hsp90 in the proteostatic mechanisms of photoreceptors and elaborates on its function when retinal homeostasis is disturbed. It also discusses the impact of Hsp90 on retinal diseases through its interaction with specific client proteins.
Article
Biochemistry & Molecular Biology
Jian Liu, Wanyue Xu, Kaijie Wang, Fanrui Chen, Ling Ren, Jingjie Xu, Ke Yao, Xiangjun Chen
Summary: Congenital cataract, caused by abnormal aggregation of crystallin, is a common disease that leads to blindness in newborns worldwide. The L116P mutation in β B1-CRY affects the protein's structural stability, susceptibility to amyloid fibrils aggregation, and protease degradation, potentially contributing to cataract development and associated symptoms.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Biochemistry & Molecular Biology
Kaushik Bhattacharya, Didier Picard
Summary: The Hsp70 and Hsp90 molecular chaperone systems in eukaryotes are crucial for protein homeostasis under normal and stressed conditions, exhibiting both physical and functional interactions to maintain cellular proteostasis. Co-chaperones like Hop and Sti1 play a key role in facilitating substrate transfer from Hsp70 to Hsp90. Interestingly, while eukaryotes rely on the canonical Hsp70-Hop-Hsp90 ternary chaperone complex for optimal maturation and stability of specific clients, prokaryotes can form a binary chaperone complex without Hop, displaying enhanced protein folding and anti-aggregation activities.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Physics, Multidisciplinary
Anasua Mukhopadhyay, Iliya D. Stoev, David. A. King, Kamendra P. Sharma, Erika Eiser
Summary: In this study, Dynamic Light Scattering (DLS) and DLS-based microrheology were used to investigate the formation of amyloid fibrils in weakly denaturing conditions and the protective effect of polymer-surfactant conjugation on protein aggregation. The results showed that native bovine serum albumin (nBSA) forms filamentous aggregates with amyloid-like structure, while BSA conjugated with polymer-surfactants remains dispersed and undergoes only minor changes in folding state. Time-resolved DLS-based microrheology studies demonstrated the viscoelastic properties of the nBSA aggregates, which formed an entangled network. Furthermore, heating native BSA solutions resulted in self-standing films with a hierarchical self-assembly of amyloid fibrils.
FRONTIERS IN PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Zeyaul Islam, Mohamed H. Ali, Anton Popelka, Raghvendra Mall, Ehsan Ullah, Janarthanan Ponraj, Prasanna R. Kolatkar
Summary: Amyloid fibrillation, related to various neurological disorders, was studied by examining lysozyme fibrillation using nano-infrared spectroscopy (nanoIR). The study showed that lysozyme transformed into mainly parallel beta-sheets in its fibrillar structure, and nanoIR can complement other biophysical studies in analyzing the aggregation process for potential therapeutic design against amyloid disorders.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
David C. Thorn, Elmira Bahraminejad, Aidan B. Grosas, Tomas Koudelka, Peter Hoffmann, Jitendra P. Mata, Glyn L. Devlin, Margaret Sunde, Heath Ecroyd, Carl Holt, John A. Carver
Summary: Bovine milk alpha(S2)-casein, an intrinsically disordered protein, readily forms amyloid fibrils in vitro. The disulfide-linked dimer of this protein has a greater propensity to form amyloid fibrils than its monomeric counterpart when incubated at 37 degrees Celsius. Experimental results suggest that the dimer structure of this protein exhibits amyloid-like characteristics.
BIOPHYSICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Caitlin L. Johnston, Nicholas R. Marzano, Bishnu P. Paudel, George Wright, Justin L. P. Benesch, Antoine M. van Oijen, Heath Ecroyd
Summary: Research on small heat shock proteins (sHsps) focuses on their molecular mechanisms and interactions with misfolded proteins, utilizing single-molecule fluorescence to determine the stoichiometries of complexes formed with client proteins like chloride intracellular channel 1. This approach reveals a two-step mechanism by which sHsps like alphaB-crystallin prevent protein aggregation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Shannon McMahon, Steven Bergink, Harm H. Kampinga, Heath Ecroyd
Summary: The study shows that DNAJB proteins can inhibit protein aggregation by supporting the Hsp70-dependent degradation pathway, different from the mechanism of preventing fibrillar aggregation. The research also found that DNAJB6 and DNAJB8 have two distinct regions for binding substrates.
JOURNAL OF CELL SCIENCE
(2021)
Article
Chemistry, Medicinal
Jessica Kho, P. Chi Pham, Suhyeon Kwon, Alana Y. Huang, Joel P. Rivers, Huixin Wang, Heath Ecroyd, W. Alexander Donald, Shelli R. McAlpine
Summary: This study presents the development of small molecule peptides derived from the N-terminal sequence of Hsp27 protein, demonstrating the ability to directly regulate protein aggregation, offering a new approach for drug development in controlling protein aggregation.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Cell Biology
Rebecca San Gil, Benjamin E. Clarke, Heath Ecroyd, Bernadett Kalmar, Linda Greensmith
Summary: The study examined regional variations in the expression of Hsp25 in glia of the central nervous system, revealing that Hsp25 expression is not upregulated under acute or chronic stress conditions.
Review
Cell Biology
Shenae L. Cafe, Brett Nixon, Heath Ecroyd, Jacinta H. Martin, David A. Skerrett-Byrne, Elizabeth G. Bromfield
Summary: Protein homeostasis is crucial for the function and viability of fully differentiated, long-lived cells, including neurons and germ cells. Understanding and maintaining protein homeostasis is vital for successful fertilization and reproductive health. This review highlights the importance of proteostasis in germline cells and its potential impact on aging and fertility.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Henry M. Sanders, Blagojce Jovcevski, Michael T. Marty, Tara L. Pukala
Summary: The study demonstrates that lipid membrane composition influences the aggregation of misfolding proteins and the efficacy of amyloid inhibitors. Different mechanisms were observed for two well-known polyphenol inhibitors in the presence of lipid membranes, highlighting the importance of considering lipid environments in amyloid inhibitor design.
Article
Biochemistry & Molecular Biology
Kristian Claesson, Yee Lian Chew, Heath Ecroyd
Summary: This study describes a simple and rapid flow cytometry-based approach for quantifying fluorescently tagged inclusions in whole worm lysate. It is applicable to various models of aggregation and can monitor the dynamics of inclusion formation.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Biochemical Research Methods
Stephanie Nguyen, Blagojce Jovcevski, Tara L. Pukala, John B. Bruning
Summary: This study presents the structure of a fungal GMP synthase, showing its differences with the human homologue. The fungal GMP synthase adopts a dimeric state and exhibits key differences in substrate binding sites compared to the human homologue. Additionally, the inhibitory activities of certain compounds against the fungal GMP synthase are demonstrated.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Stephanie Nguyen, Blagojce Jovcevski, Jia Q. Truong, Tara L. Pukala, John B. Bruning
Summary: Enolase is a metabolic enzyme that plays a critical role in cellular energy production and also functions as a virulence factor in pathogenic bacteria and fungi. This study focused on the structure and interactions of enolase from Aspergillus fumigatus. The researchers determined the crystal structure of enolase and its binding to substrates and products, and they built a model of the enolase-plasminogen complex. These findings provide insights into the mechanisms of virulence and have potential implications for the development of antifungal drugs.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Emily E. Selig, Roberta J. Lynn, Courtney O. Zlatic, Yee-Foong Mok, Heath Ecroyd, Paul R. Gooley, Michael D. W. Griffin
Summary: The crystallin domain of human sHSPs interacts with amyloid fibrils to inhibit their elongation and joining. This interaction is sensitive to fibril concentration, suggesting a regulatory role in fibril dynamics.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Medicinal
Damian L. Stachura, Stephanie Nguyen, Steven W. Polyak, Blagojce Jovcevski, John B. Bruning, Andrew D. Abell
Summary: In this study, the synthesis and assay of N1-diphenylmethyl triazole-based analogues were reported, which showed potent inhibitory activity against Staphylococcus aureus. The findings have important clinical implications for combating blood-based infections caused by Staphylococcus aureus.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Medicinal
Damian L. Stachura, Stephanie Nguyen, Steven W. Polyak, Blagojce Jovcevski, John B. Bruning, Andrew D. Abell
Summary: The rise of multidrug-resistant bacteria has created an urgent need for new antibiotics, and one potential target is the enzyme biotin protein ligase (BPL). In this study, a new series of inhibitors of Staphylococcus aureus BPL (SaBPL) were designed, synthesized, and tested. Two particular compounds, triazoles 13 and 14, showed strong inhibition against SaBPL with Ki values of 10 +/- 2 and 30 +/- 6 nM, respectively, likely through hydrogen bonding interactions with amino acid residues S128 and N212 of SaBPL.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Analytical
RiverJ. Pachulicz, Long Yu, Blagojce Jovcevski, Vincent Bulone, Tara L. Pukala
Summary: This study investigates the use of direct injection ion mobility-mass spectrometry (MS) as a rapid analytical tool to characterize the structural features of anthocyanins in red cabbage extracts. The method allows for the identification of structurally similar anthocyanins and their isobars, providing comprehensive structural information for plant extracts. The approach has potential applications in determining the nutritional value of plants and aiding in drug discovery pipelines.
ACS MEASUREMENT SCIENCE AU
(2023)
Article
Biochemistry & Molecular Biology
River J. Pachulicz, Long Yu, Blagojce Jovcevski, Vincent Bulone, Tara L. Pukala
Summary: Magenta lilly pilly fruits, which are native to Australia, contain phytochemicals that have beneficial effects on human health, such as antioxidant, neuroprotective, and antimicrobial activities. The primary component in these fruits is anthocyanins, which are present in higher abundance compared to traditional anthocyanin-containing plants. These findings suggest that magenta lilly pilly fruits have the potential for various applications due to their high phenolic content and beneficial biological properties.