Review
Biochemistry & Molecular Biology
Jin-Beom Si, Bokyung Kim, Jin Hae Kim
Summary: TTR is a crucial transporter of thyroid hormone and retinol binding protein in human plasma and cerebrospinal fluid, yet it is also known for its amyloidogenic nature leading to various amyloidoses. Research has shown that decreased stability of TTR's native tetrameric conformation is the main cause of these diseases, and recent multidisciplinary investigations have shed light on the mechanistic details of TTR amyloidogenic transformation. Special emphasis has been placed on identifying novel structural features in amyloidogenic species of TTR and discussing the proteolysis-induced fragmentation mechanism that promotes TTR amyloidosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sanduni Wasana Jayaweera, Solmaz Surano, Nina Pettersson, Elvira Oskarsson, Lovisa Lettius, Anna L. Gharibyan, Intissar Anan, Anders Olofsson
Summary: The study demonstrates that TTR can interfere with IAPP amyloid-formation, prolonging the lag-phase and impairing elongation. The interfering ability correlates inversely with the thermodynamic stability of TTR, but not with kinetic stability. TTR's interference ability remains effective in the low pH environment of IAPP-containing granules, but TTR-stabilizing drugs partially weaken its efficacy.
Article
Biochemistry & Molecular Biology
Jayakrishna Shenoy, Alons Lends, Melanie Berbon, Muhammed Bilal, Nadia El Mammeri, Mathilde Bertoni, Ahmad Saad, Estelle Morvan, Axelle Grelard, Sophie Lecomte, Francois-Xavier Theillet, Alexander K. Buell, Brice Kauffmann, Birgit Habenstein, Antoine Loquet
Summary: Aberrant aggregation of TDP-43 protein is linked to lethal neurodegenerative diseases. Using a combination of techniques, we found that different fragments of TDP-43 adopt distinct polymorphic structures in their amyloid fibrillar state. Our study reveals that removal of a small portion of the low-complexity sequence can lead to amyloid fibrils with similar macroscopic features but different local structural arrangements.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Multidisciplinary Sciences
Maximo Sanz-Hernandez, Joseph D. Barritt, Jens Sobek, Simone Hornemann, Adriano Aguzzi, Alfonso De Simone
Summary: The T183A variant of human PrP significantly enhances aggregation propensity, leading to amyloid formation under physiological conditions by the sole C-terminal domain of the protein. The study identified the structural characteristics of the misfolded intermediate promoting aggregation of T183A huPrP and the interactions preventing the population of this species in the wild-type protein, supporting the use of POM antibodies to suppress the aggregation of this amyloidogenic mutant.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Polymer Science
Stepan A. Ostanin, Maxim Mokeev, Dmitry Pikhurov, Aleksandr S. Sakhatskii, Vjacheslav V. Zuev
Summary: Aromatic-oxyaliphatic polyurethanes were synthesized with varying mass fractions of components, including fluorinated fragments, and their rigid domains were found to be formed by units containing urethane bonds as well as oxyethylene fragments. The urethane bonds and oxyethylene fragments were incorporated into both rigid and soft phases, showing good agreement with the Cooper and Tobolsky model under specific solubility parameters for different segments.
Article
Biochemistry & Molecular Biology
Irena Roterman, Katarzyna Stapor, Leszek Konieczny
Summary: The structural transformation producing amyloids provides new insights into the protein folding problem. Analysis of the polymorphic structures of a-synuclein amyloid reveals a dominant distribution consistent with the micelle-like system. This ordering of hydrophobicity distribution covers a spectrum from micelle-like forms to structures with different patterns, all influenced by the water environment and the common tendency of certain fragments of a-synuclein to accept micelle-like structuralization.
Review
Biochemistry & Molecular Biology
Liisa Lutter, Liam D. Aubrey, Wei-Feng Xue
Summary: Predicting the highly ordered three-dimensional structures of amyloid protein fibrils from their monomeric self-assembly precursors remains a challenging aspect of the classical protein folding problem, due to the polymorphic nature of amyloid assembly. Understanding the diversity and individuality of amyloid structures, as well as the link to biology and disease phenotypes, is essential. Current research focuses on resolving the structural basis and biological consequences of polymorphic amyloid assemblies using various techniques such as cryo-EM, ssNMR, and AFM.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Cell Biology
Elzbieta Wieczorek, Andrzej Ozyhar
Summary: TTR plays multiple roles in the body, serving as an indicator of nutrition status and a neuroprotective factor. The structural stability of TTR is closely linked to oxidative stress and Ca2+, which may contribute to the development of TTR-related diseases.
Article
Chemistry, Physical
Taiana L. E. Pereira, Kevin J. Sanders, Danielle L. Smiley, James F. Britten, Gillian R. Goward
Summary: 7Li solid-state nuclear magnetic resonance (ssNMR) reveals unexpected structural complexity and substantive changes in the local dynamics of lithium exchange in monoclinic LiFeV2O7 as a function of electrochemical lithium insertion. The study shows that the crystal structure and lithium arrangement in LiFeV2O7 undergo significant changes during lithium insertion, resulting in extra signals in the 7Li ssNMR spectrum. The observed changes in lithium-ion dynamics are consistent with an increase in lithium-ion mobility as observed by 2D EXSY experiments.
CHEMISTRY OF MATERIALS
(2022)
Review
Biochemistry & Molecular Biology
Yuji Goto, Masahiro Noji, Kichitaro Nakajima, Keiichi Yamaguchi
Summary: Supersaturation refers to the non-equilibrium state of a solution where the solute concentration exceeds its thermodynamic solubility. Recent evidence suggests that supersaturation plays a critical role in amyloid fibril formation and the onset of amyloidosis. In addition to structural studies, research on solubility and supersaturation is essential for a comprehensive understanding of amyloid fibrils and their roles in amyloidosis, as well as for developing therapeutic strategies.
Article
Chemistry, Multidisciplinary
Shengnan Zhang, Juan Li, Qianhui Xu, Wencheng Xia, Youqi Tao, Chaowei Shi, Dan Li, ShengQi Xiang, Cong Liu
Summary: Many amyloid fibrils associated with neurodegenerative diseases consist of an ordered fibril core and disordered terminal regions. In this study, we used solid-state NMR and cryo-EM techniques to explore the intact structure of an alpha-syn fibril and studied its conformational dynamics upon binding to the LAG3 receptor. Our findings reveal the synergistic conformational transition of the intrinsically disordered terminal regions of alpha-syn, shedding light on the role of these regions in regulating amyloid fibril structure and pathology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Dalia Naser, Michael Tarasca, Bruna Siebeneichler, Anna Schaefer, Harmeen K. Deol, Tyler G. B. Soule, Johnathan Almey, Susan Kelso, Gyana G. Mishra, Hilary Simon, Elizabeth M. Meiering
Summary: Protein aggregation plays a central role in aging, disease and biotechnology. This study used NMR quenched amide hydrogen/deuterium exchange, FTIR, and Congo red binding to analyze cellular inclusion bodies of immature human superoxide dismutase mutants. The results revealed multiple aggregation-prone regions in SOD1 and provided insights into the pathways of aggregation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Cardiac & Cardiovascular Systems
Rene Rettl, Christopher Mann, Franz Duca, Theresa-Marie Dachs, Christina Binder, Luciana Camuz Ligios, Lore Schrutka, Daniel Dalos, Matthias Koschutnik, Carolina Dona, Andreas Kammerlander, Dietrich Beitzke, Christian Loewe, Silvia Charwat-Resl, Christian Hengstenberg, Johannes Kastner, Roza Badr Eslam, Diana Bonderman
Summary: Tafamidis can delay the progression of myocardial amyloidosis in ATTR-CM patients, providing structural, functional, and clinical benefits. Cardiac magnetic resonance imaging, including measurement of ECV, may be appropriate for disease-specific therapy monitoring.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
(2022)
Article
Multidisciplinary Sciences
Irina Iakovleva, Michael Hall, Melanie Oelker, Linda Sandblad, Intissar Anan, A. Elisabeth Sauer-Eriksson
Summary: The study used cryo-EM to analyze the structure of vitreous body ATTR fibrils from an ATTR patient's eye, revealing differences from previously studied heart fibrils with the same mutation, indicating variations in ATTR protein structure and assembly in type A fibrils among patients with the same mutation. By analyzing amino acid interfaces, a mechanism for the structural conversion of TTR into fibrillar form was proposed.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Adam S. Knier, Emily E. Davis, Hannah E. Buchholz, Jane E. Dorweiler, Lauryn E. Flannagan, Anita L. Manogaran
Summary: In patients with ATTR, the misfolding and aggregation of TTR protein leads to the destruction of peripheral nervous tissue. By using a humanized yeast system, researchers found that a variant of Hsp104 can change the characteristics of TTR aggregates, shifting them from toxic oligomers to more stable larger aggregates.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemical Research Methods
Adam R. Altenhof, Zhehong Gan, Robert W. Schurko
Summary: The CPMG pulse sequence is crucial for enhancing signal of solid-state NMR spectra influenced by various factors, and the effects of dipolar couplings, short refocusing pulses, and experimental conditions on T-2 lifetimes have been well documented.
JOURNAL OF MAGNETIC RESONANCE
(2022)
Article
Materials Science, Ceramics
Yiqing Xia, Hao Chen, Ivan Hung, Zhehong Gan, Sabyasachi Sen
Summary: The structure of (ZnO)(x)(P2O5)(100-x) glasses with 35 <= x <= 67 was investigated using P-31 and ultra-high field Zn-67 NMR spectroscopy, revealing changes in phosphorus and zinc coordination numbers, as well as trends in T-g and fragility index m with increasing Zn content.
JOURNAL OF NON-CRYSTALLINE SOLIDS
(2022)
Article
Chemistry, Physical
Xiang Li, Xinhao Li, Lisa Monluc, Benjamin Chen, Mingxue Tang, Po-Hsiu Chien, Xuyong Feng, Ivan Hung, Zhehong Gan, Alexander Urban, Yan-Yan Hu
Summary: This study investigates the lattice oxygen redox reactions in layered Li-rich transition metal oxide cathodes using O-17 NMR technique. The results demonstrate that stacking faults can enhance the participation of lattice oxygen, thereby improving the capacity and energy density of the cathodes.
ADVANCED ENERGY MATERIALS
(2022)
Article
Geriatrics & Gerontology
Mathew S. Maurer, Dia Smiley, Eli Simsolo, Fabrizio Remotti, Angela Bustamante, Sergio Teruya, Stephen Helmke, Andrew J. Einstein, Ronald Lehman, Jon T. Giles, Jeffery W. Kelly, Felix Tsai, William S. Blaner, Pierre-Jacques Brun, Ron Riesenburger, James Kryzanski, Cindy Varga, Ayan R. Patel
Summary: Lumbar spinal stenosis (LSS) is a common reason for spine surgery in older adults, with amyloid detected in over one third of patients, especially in those over 75 years old. Age, clinical symptoms, cardiac biomarkers, and other parameters did not differ significantly between patients with and without amyloid.
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Cecilia Monteiro, Jaleh S. Mesgarzadeh, Joao Anselmo, Joana Fernandes, Marta Novais, Carla Rodrigues, David L. Powers, Evan T. Powers, Teresa Coelho, Jeffery W. Kelly
Summary: This study explored the relationship between TTR stabilization markers and clinical efficacy of tafamidis treatment. The results showed an increase in native TTR concentration and a decrease in non-native TTR concentration. However, changes in native and non-native TTR levels were not correlated with clinical response to tafamidis. Successful tafamidis therapy requires moderate TTR stabilization, and male patients may benefit from higher doses of tafamidis.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Felix J. J. Tsai, Luke T. T. Nelson, Gabriel M. M. Kline, Marcus Jager, John L. L. Berk, Yoshiki Sekijima, Evan T. T. Powers, Jeffery W. Kelly
Summary: This study investigated the plasma concentrations of diflunisal and its efficacy in treating TTR polyneuropathy, finding that at a certain concentration, diflunisal can effectively slow down TTR dissociation rate and inhibit aggregation.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Chemistry, Physical
Ieva Goldberga, Nicholai D. Jensen, Christele Combes, Frederic Mentink-Vigier, Xiaoling Wang, Ivan Hung, Zhehong Gan, Julien Trebosc, Thomas-Xavier Metro, Christian Bonhomme, Christel Gervais, Danielle Laurencin
Summary: This study investigates the possibility of enriching O-17 isotopes in water molecules within hydrated biominerals using liquid assisted grinding. The results show that the labelled water molecules are mainly located at the core of the crystal structures and can enter the lattice through dissolution/recrystallization or diffusion. This work highlights the importance of high-resolution O-17 NMR in understanding the roles of water as a grinding agent and as a reagent for isotopic enrichment.
FARADAY DISCUSSIONS
(2023)
Article
Chemistry, Multidisciplinary
Yuuki Wittmer, Khaled M. Jami, Rachelle K. Stowell, Truc Le, Ivan Hung, Dylan T. Murray
Summary: Protein domains biased toward a few amino acid types play a crucial role in the formation of biomolecular condensates. These compartments are formed by molecules with various movements and structural order. Missense mutations can increase the persistence lifetimes or structural order of condensates, which are associated with pathological protein aggregation. In the study of stress granules related to neurodegenerative diseases, the liquid droplets of protein are transformed into beta-strand rich fibrils. The research focuses on the molecular mechanism of the rigidification of liquid droplets and the influence of disease mutations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Vinicius Martins, Bryan E. G. Lucier, Kuizhi Chen, Ivan Hung, Zhehong Gan, Christel Gervais, Christian Bonhomme, Heng-Yong Nie, Wanli Zhang, Yining Huang
Summary: Porous metal-organic frameworks (MOFs) have diverse applications in various fields, and post synthetic modification (PSM) approaches can enhance their properties. In this study, high-field solid-state NMR techniques were used to gain molecular-level insights into a prototypical aluminum MOF and its interactions with metal guests. The results provide detailed information about the oxygen environment, intermolecular interactions, and host-guest connectivity in the MOF.
CHEMISTRY OF MATERIALS
(2023)
Article
Chemistry, Inorganic & Nuclear
Molly Wagner, Roberta Pigliapochi, Valeria Di Tullio, Jaclyn Catalano, Nicholas Zumbulyadis, Silvia A. Centeno, Xiaoling Wang, Kuizhi Chen, Ivan Hung, Zhehong Gan, Michael R. Dworzak, Glenn P. A. Yap, Cecil Dybowski
Summary: A series of medium- and long-chain zinc carboxylates were analyzed using ultra-high-field Zn-67 NMR, C-13 NMR, and FTIR spectroscopy. The single-crystal X-ray diffraction structures of zinc nonanoate, zinc decanoate, and zinc oleate were also reported for the first time. The NMR and X-ray diffraction data suggest the existence of three distinct geometric groups for the carboxylates. This study provides a future direction for the use of dynamic nuclear polarization (DNP)-NMR-based minimally invasive methods to test artwork for the presence of zinc carboxylates.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Multidisciplinary
Wanli Zhang, Alia Hassan, Jochem Struppe, Martine Monette, Ivan Hung, Zhehong Gan, Vinicius Martins, Victor Terskikh, Yining Huang
Summary: By combining new cryogenic MAS probe technology and conducting NMR experiments at a high magnetic field, the challenges of low sensitivity in Zn-67 solid-state NMR have been overcome, leading to remarkable signal enhancement and providing enhanced information for MOF characterization.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Ivan Hung, Wenping Mao, Eric G. Keeler, Robert G. Griffin, Peter L. Gor'kov, Zhehong Gan
Summary: High sensitivity and resolution solid-state NMR methods are developed for selecting hydrogen-bonded N-15-O-17 pairs in peptides, aiding protein secondary and tertiary structure determination. Enhanced sensitivity is achieved through indirect H-1 detection under fast MAS and stronger relayed dipole couplings.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Yijue Xu, Miriam Calabrese, Nicola Demitri, Andrea Pizzi, Tamali Nag, Ivan Hung, Zhehong Gan, Giuseppe Resnati, David L. Bryce
Summary: The bonding between rhenium and organic perrhenates is investigated using Re-185/187 solid-state NMR and Re-185/187 NQR techniques. The quadrupolar couplings of Re-185/187 can distinguish MaB samples from control samples, and their precise values are affected by the shear strain of ReO4- anions.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Yijue Xu, Miriam Calabrese, Nicola Demitri, Andrea Pizzi, Tamali Nag, Ivan Hung, Zhehong Gan, Giuseppe Resnati, David L. Bryce
Summary: In this study, the bonding between rhenium and the matrix in a set of organic perrhenates was investigated using Re-185/187 solid-state NMR and Re-185/187 NQR techniques. The quadrupolar couplings of Re-185/187 were able to distinguish between MaB samples and control samples, and their precise values were determined by the shear strain of the ReO4- anions.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Cesar Leroy, Thomas-Xavier Metro, Ivan Hung, Zhehong Gan, Christel Gervais, Danielle Laurencin
Summary: The formation and structure of zinc terephthalate compounds were studied using mechanochemistry and operando Raman spectroscopy. Three intermediates were identified during the ball-milling synthesis of Zn3(OH)4(BDC). NMR crystallography and DFT calculations were used to refine the crystallographic structures of these compounds, and 17O NMR analyses provided valuable insights into the presence of defect sites and hydrogen bonding networks. Deuterated precursors were also introduced for observing specific transformations during operando Raman spectroscopy. These approaches contribute to a better understanding of complex coordination networks and MOFs.
CHEMISTRY OF MATERIALS
(2022)
