Review
Biochemistry & Molecular Biology
Roberto Maggio, Irene Fasciani, Francesco Petragnano, Maria Francesca Coppolino, Marco Scarselli, Mario Rossi
Summary: Unstructured regions in functional proteins, specifically the i3 loop and C-terminus in G protein-coupled receptors (GPCRs), have been recognized as crucial elements in GPCR function and regulation. They play critical roles in allosterically regulating GPCR activation, as autoregulators in receptor coupling specificity, and in facilitating receptor stability and interactions with intracellular protein partners.
Article
Multidisciplinary Sciences
Tomoyuki Yoshida, Atsushi Yamagata, Ayako Imai, Juhyon Kim, Hironori Izumi, Shogo Nakashima, Tomoko Shiroshima, Asami Maeda, Shiho Iwasawa-Okamoto, Kenji Azechi, Fumina Osaka, Takashi Saitoh, Katsumi Maenaka, Takashi Shimada, Yuko Fukata, Masaki Fukata, Jumpei Matsumoto, Hisao Nishijo, Keizo Takao, Shinji Tanaka, Shigeo Okabe, Katsuhiko Tabuchi, Takeshi Uemura, Masayoshi Mishina, Hisashi Mori, Shuya Fukai
Summary: Mutations of Neuroligin 3 (NLGN3) have been linked to autism spectrum disorder (ASD). Researchers have identified a new interaction between NLGN3 and a splice variant of protein tyrosine phosphatase delta (PTP delta) and its impact on social behavior development in mice. The study suggests that both canonical and non-canonical NLGN3 pathways compete and regulate the development of sociality.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Awa Diop, Paola Pietrangeli, Caterina Nardella, Valeria Pennacchietti, Livia Pagano, Angelo Toto, Mariana Di Felice, Sara Di Matteo, Lucia Marcocci, Francesca Malagrino, Stefano Gianni
Summary: SPOP is an E3 ubiquitin ligase adaptor protein that mediates the ubiquitination of several substrates. It is responsible for regulating both degradable and nondegradable polyubiquitination of various substrates with diverse biological functions. The recognition of SPOP and its physiological partners is mediated by two protein-protein interaction domains.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Chloe A. N. Gerak, Sophia Y. Cho, Maxim Kolesnikov, Mark Okon, Michael E. P. Murphy, Richard B. Sessions, Michel Roberge, Lawrence P. McIntosh
Summary: ETV6 is a transcriptional repressor that self-associates through its PNT domain to aid DNA binding, often involved in chromosomal translocations generating active oncogenic proteins. Studies demonstrate that targeting the hydrophobic or charged regions with small molecules could potentially inhibit ETV6 PNT domain polymerization.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Applied
Sivan Gelley, Hodaya Lankry, Jovana Glusac, Ayelet Fishman
Summary: Results suggest that yeast-derived patatin properties are comparable to those from potatoes, indicating potential use in various plant-based products.
Article
Multidisciplinary Sciences
Elisa Duregotti, Christina M. Reumiller, Ursula Mayr, Maria Hasman, Lukas E. Schmidt, Sean A. Burnap, Konstantinos Theofilatos, Javier Barallobre-Barreiro, Arne Beran, Maria Grandoch, Alessandro Viviano, Marjan Jahangiri, Manuel Mayr
Summary: This study used proteomics analysis to compare the secretory profiles of perivascular fat with other fat depots and identified neuronal growth regulator 1 as an adipocyte-derived neurotrophic factor. Decreased secretion of neuronal growth regulator 1 in obesity leads to a loss of sympathetic innervation of adipose depots in mice.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Christine Belloir, Marine Brule, Lucie Tornier, Fabrice Neiers, Loic Briand
Summary: Sweet taste perception is mediated by a heterodimeric receptor formed by TAS1R2 and TAS1R3 subunits. Researchers overexpressed and purified hTAS1R2 to study its structure and ligand binding properties, showing its capability to bind high potency sweeteners. This study provides a new experimental strategy for identifying new sweeteners or taste modulators acting on hTAS1R2, and is essential for future structural and biophysical studies.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Lorenzo Soini, Seppe Leysen, Jeremy Davis, Marta Westwood, Christian Ottmann
Summary: SLP76 is an important adaptor protein that interacts with 14-3-3 proteins to control TCR signaling through phosphorylation on Ser376. By determining the crystal structure and characterizing the binding properties, researchers have laid the foundation for drug design efforts targeting the 14-3-3/SLP76 interaction.
Article
Biochemistry & Molecular Biology
Laura Kind, Arne Raasakka, Janne Molnes, Ingvild Aukrust, Lise Bjorkhaug, Pal Rasmus Njolstad, Petri Kursula, Thomas Arnesen
Summary: In this study, the structure and function of HNF-1A were analyzed, and several pathogenic variants related to MODY3 were identified. These findings are important for precise diagnosis and treatment of diabetes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Giulia Murtas, Giorgia Letizia Marcone, Alessio Peracchi, Erika Zangelmi, Loredano Pollegioni
Summary: The study focused on the activity of the human enzyme hPHGDH in the reversible dehydrogenation process and highlighted the effects of substrate competition and different conformations on the enzyme. It was found that coagonists related to L-serine metabolism did not inhibit the enzyme, suggesting potential novel approaches for modulating L-serine levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Jayendrakishore Tanjore Ramanathan, Tomas Zarybnicky, Pauliina Filppu, Hector J. Monzo, Outi Monni, Topi A. Tervonen, Juha Klefstrom, Laura Kerosuo, Satu Kuure, Pirjo Laakkonen
Summary: The immunoglobulin superfamily member IGSF3 plays a crucial role in the formation and maintenance of the enteric nervous system during embryonic development. Knocking out Igsf3 results in impaired migration of vagal neural crest cells and abnormal innervation of the intestine, leading to reduced muscularis externa thickness, decreased enteric neuron number, and misalignment of neurons and smooth muscle cells in the developing intestinal villi.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Xu Zhao, Jiancong Lu, Xuebing Chen, Zhengxiang Gao, Cui Zhang, Chuanxiang Chen, Dongfang Qiao, Huijun Wang
Summary: The study identified the molecular mechanisms of METH-induced neuronal programmed necrosis, showing that RIP3 plays a crucial role in the process and could be a potential therapeutic target for METH-induced neurotoxicity.
Article
Multidisciplinary Sciences
Mohanraj Gopalswamy, Tobias Kroeger, David Bickel, Benedikt Frieg, Shahina Akter, Stephan Schott-Verdugo, Aldino Viegas, Thomas Pauly, Manuela Mayer, Julia Przibilla, Jens Reiners, Luitgard Nagel-Steger, Sander H. J. Smits, Georg Groth, Manuel Etzkorn, Holger Gohlke
Summary: This study characterized the interaction between the small-molecule compound 7.44 and the NHR2 domain of the oncogenic fusion protein RUNX1/ETO. The results showed that 7.44 interfered with the stability of NHR2 tetramer and increased the population of NHR2 dimer. The binding mechanism of 7.44 to NHR2 was elucidated through NMR spectroscopy and molecular dynamics simulations. It was also demonstrated that 7.44 had favorable physicochemical, pharmacokinetic, and toxicological properties. Overall, this compound shows potential as a lead for targeted therapy of t(8;21) AML.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Zhiqiang Hou, Dailu Chen, Bryan D. Ryder, Lukasz A. Joachimiak
Summary: The pathogenesis of tauopathies involves converting tau monomers into pathological conformers that recruit native tau into growing assemblies. Small soluble tau seeds may be responsible for driving the assembly of pathological tau in vitro, in cells, and in vivo. Through biochemical and biophysical approaches, it has been shown that recombinant soluble tau seeds derived from heparin treatment are predominantly monomeric and have the ability to nucleate aggregation of inert forms of tau in vitro and in cells.
SCIENTIFIC REPORTS
(2021)
Article
Engineering, Electrical & Electronic
Ke Wang, Yan Liu, Deyong Chen, Junbo Wang, Jian Chen
Summary: This article develops a microfluidic platform to characterize the biomechanical and bioelectrical parameters of individual cells simultaneously. It quantifies the inherent biophysical parameters of various cell types and improves the classification success rates using these parameters.
IEEE TRANSACTIONS ON ELECTRON DEVICES
(2022)
Article
Biochemistry & Molecular Biology
Petr Konarev, Melissa A. Graewert, Cy M. Jeffries, Masakazu Fukuda, Taisiia A. Cheremnykh, Vladimir V. Volkov, Dmitri Svergun
Summary: SAXS is commonly used for structural analysis of biological macromolecules in solution, and combining SAXS with chromatography setups has become popular in research. The computer program EFAMIX, based on evolving factor analysis (EFA), efficiently restores scattering and concentration profiles of components from mixed SAXS data, proving useful for interpretation and analysis of fractions in the sample.
Biographical-Item
Chemistry, Multidisciplinary
Dmitri Svergun, Jill Trewhella
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2022)
Article
Multidisciplinary Sciences
Oren Yakovian, Julia Sajman, Michal Alon, Rand Arafeh, Yardena Samuels, Eilon Sherman
Summary: NRas is a crucial mediator of the mitogenic pathway in both normal and cancer cells, and its signaling is regulated by dynamic interactions with functional clusters of BRAF or other related proteins at the plasma membrane.
Article
Biochemistry & Molecular Biology
Iain M. Hay, Maria Shamin, Eve R. Caroe, Ahmed S. A. Mohanned, Dmitri I. Svergun, Cy M. Jeffries, Stephen C. Graham, Hayley J. Sharpe, Janet E. Deane
Summary: Type IIB receptor protein tyrosine phosphatases mediate cell adhesion and signaling through their extracellular and cytoplasmic domains, respectively. The crystal structure of PTPRK has revealed an intermembrane adhesion mode consistent with other family members. Comparison with PTPRM structure suggests that conformational differences between the domains may contribute to homophilic specificity. Analysis of the full-length PTPRM and PTPRK proteins using small-angle X-ray scattering reveals rigid extended conformations and one residue difference at the interaction interface that affects dimer formation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Goksin Liu, Erhan Ekmen, Farzaneh Jalalypour, Haydyn D. T. Mertens, Cy M. Jeffries, Dmitri Svergun, Ali Rana Atilgan, Canan Atilgan, Zehra Sayers
Summary: This study combines molecular dynamics (MD) simulations with small angle x-ray scattering (SAXS) measurements to investigate the range of conformations and populations of a pH/ionic strength (IS) sensitive protein. The protein studied is the periplasmic ferric binding protein A (FbpA) involved in iron capture from higher organisms by bacteria. The study reveals the detectable changes in conformational distribution of FbpA under different conditions, but detection of conformational changes due to point mutation D52A and changes in ionic strength has been challenging.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Gabriela Guedez, Gabriele Loers, Cy M. Jeffries, Sandra Kozak, Rob Meijers, Dmitri I. Svergun, Melitta Schachner, Christian Loew
Summary: The cell adhesion molecule L1 plays crucial roles in neural development, regeneration, synaptic plasticity, and tumor cell migration. L1 is a member of the immunoglobulin superfamily and consists of Ig-like domains and fibronectin type III homologous repeats. The second Ig-like domain is involved in cell binding, and the fibronectin type III homologous repeats contribute to signal transduction.
Article
Biochemistry & Molecular Biology
Jing Liu, Rongqing Yuan, Wei Shao, Jitong Wang, Israel Silman, Joel L. Sussman
Summary: This article discusses the value of three newly developed programs for predicting protein structures in comparing newly born proteins and never born proteins, and validates the feasibility of this method by comparing the predicted results with experimental data.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemical Research Methods
Masakazu Fukuda, Melissa A. Graewert, Cy M. Jeffries, Dmitri I. Svergun, Tadao Yamazaki, Akiko Koga, Yuji Yamanaka
Summary: This study investigates the acidic variants of therapeutic monoclonal antibodies (mAbs) using a refolding approach. The results showed that these acidic variants are conformational variants with minor and localized conformational changes.
ANALYTICAL BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Stefano Da Vela, Giovanni Saudino, Francesca Lucarelli, Lucia Banci, Dmitri I. Svergun, Simone Ciofi-Baffoni
Summary: In humans, the biosynthesis and trafficking of mitochondrial [4Fe-4S]2+ clusters is a highly coordinated process that requires a complex protein machinery. Two [2Fe-2S]2+ clusters are converted into a [4Fe-4S]2+ cluster on an ISCA1-ISCA2 complex. NFU1 is the accessory protein that first receives the [4Fe-4S]2+ cluster from the ISCA1-ISCA2 complex.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Mikael T. Ekvall, Isabella Gimskog, Egle Kelpsiene, Alice Mellring, Alma Mansson, Martin Lundqvist, Tommy Cedervall
Summary: The wastage of polymer products, especially plastics, has become a significant concern in nature. The breakdown of macro- and micro polymers into nano-sized particles can occur naturally or through mechanical force. In this study, it was found that both silicone and latex pacifiers released nano-sized particles after being subjected to mechanical force, with boiling increasing particle release for silicone pacifiers only. The particles from latex pacifiers were found to be acutely toxic to Daphnia magna, a freshwater filter feeding zooplankter.
Article
Virology
Zuopei Wang, Menghan He, Han He, Kyle Kilby, Roberto de Antueno, Elizabeth Castle, Nichole McMullen, Zhuoyu Qian, Tzviya Zeev-Ben-Mordehai, Roy Duncan, Chungen Pan
Summary: Vesicle-encapsulated nonenveloped viruses are a newly discovered form of nonenveloped viruses that can avoid immune detection and potentially increase systemic transmission. Avian orthoreoviruses (ARVs) are a major cause of various diseases in birds and poultry. This study revealed that ARV-infected quail cells generate small extracellular vesicles (EVs) containing electron-dense material. The EVs contain soluble virus proteins and the fusogenic p10 FAST protein and can enhance the infectivity of the virus particles.
Article
Biochemical Research Methods
Orly Dym, Nidhi Aggarwal, Yacov Ashani, Haim Leader, Shira Albeck, Tamar Unger, Shelly Hamer-Rogotner, Israel Silman, Dan S. Tawfik, Joel L. Sussman
Summary: This study investigates the factors influencing the visualization of molecular complexes of ligands with a target enzyme using a bacterial phosphotriesterase as a model. It examines the effects of molecular constructs, ligands, crystallization conditions, and space group on the visualization of ligand-protein complexes. The study reveals that protein expression tags and crystallization conditions can impact ligand binding and visualization. The competition between crystallization precipitants and ligands can also lead to false results. The study provides valuable insights into the challenges and considerations of studying crystal structures of ligand-protein complexes.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2023)
Article
Cell Biology
Ishay Wohl, Julia Sajman, Eilon Sherman
Summary: The mechanical properties of cells, such as shape, rigidity, and surface vibrations, are important for their physiological functions and disease processes. However, the relationship between the cellular state and its rigidity and surface vibrations is still not well understood. In this study, AFM measurements on T cells revealed a negative correlation between cell surface stiffness and vibrations. Blocking T-type Ca++ channels reduced cortical actin tension and increased membrane vibrations and dissipation of mechanical work in these cells.
Article
Cell Biology
Julia Sajman, Oren Yakovian, Naamit Unger Deshet, Shaked Almog, Galit Horn, Tova Waks, Anat Globerson Levin, Eilon Sherman
Summary: CARs on the surfaces of CAR-T cells exhibit nanoscale organization in clusters and segregate from CD45, which is associated with the functional activity of CAR-T cells.
Article
Nanoscience & Nanotechnology
Mikael T. Ekvall, Shanti Naidu, Martin Lundqvist, Tommy Cedervall, Maria Varendh
Summary: Nanoplastics are plastic particles broken down to extremely small sizes that have unknown effects on the human body and immune system. While existing literature focuses on scenarios involving blood, lungs, and intestine, the potential effects of plastic passing through the nose, oral cavity, and throat are currently overlooked. The tonsils, as immunologically important tissue in the oral cavity, should be studied in relation to human exposure and immune response to micro and nanoplastics. Detecting nanoplastics in the tonsils is challenging but crucial, as they can have different effects on biology compared to larger particles and bulk material.
FRONTIERS IN NANOTECHNOLOGY
(2022)