Article
Biochemistry & Molecular Biology
Brianna D. Young, Kristen M. Varney, Paul T. Wilder, Brianna K. Costabile, Edwin Pozharski, Mary E. Cook, Raquel Godoy-Ruiz, Oliver B. Clarke, Filippo Mancia, David J. Weber
Summary: The interaction between calmodulin (CaM) and the retinol uptake receptor STRA6 involves binding of a peptide derived from BP2 to the C-lobe of CaM in low free Ca2+ concentrations. As free Ca2+ levels increase, BP2 also interacts with the N-lobe of CaM. This structural rearrangement could be relevant to vitamin A transport by the full-length (CaM)-Ca-Ca-STRA6 complex as intracellular Ca2+ concentrations approach those typical of a Ca2+-signaling event.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Mrinal Bhunia, Christian Sandoval-Pauker, Mehrafshan G. Jafari, Lauren N. Grant, Michael R. Gau, Balazs Pinter, Daniel J. Mindiola
Summary: A dinuclear hafnium complex with a parent imido ligand was synthesized by reduction reaction and exhibited short Hf-N bond lengths. DFT calculations revealed the formation mechanism of the complex and showcased its reactivity with various electrophiles.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Neurosciences
Sarah Joost, Felix Schweiger, Friederike Pfeiffer, Carolin Ertl, Jonas Keiler, Marcus Frank, Markus Kipp
Summary: This study investigated the ultrastructural changes of the axon-myelin interface in the cuprizone model and found remarkable similarities between the cuprizone model and multiple sclerosis in terms of myelin characteristics. This suggests that the cuprizone model is a valuable tool to study early pathologies during lesion formation in multiple sclerosis.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biology
Daniel Flores-Mireles, Yolanda Camacho-Villasana, Madhurya Lutikurti, Aldo E. Garcia-Gurrerio, Guadalupe Lozano-Rosas, Victoria Chagoya, Emma Berta Gutierrez-Cirlos, Ulrich Brandt, Alfredo Cabrera-Orefice, Xochitl Perez-Martinez
Summary: The Cytb subunit of yeast mitochondrial complex bc is encoded in the mitochondrial genome and has eight transmembrane helices containing two hemes b. Cbp3 and Cbp6 assist in Cytb synthesis, while Cbp4 induces Cytb hemylation. Lack of Qcr7 reduces Cytb synthesis through an assembly-feedback mechanism involving Cbp3/Cbp6. Deletion of the Cytb C-region does not affect Cytb synthesis but disrupts the assembly-feedback regulation, resulting in non-respiratory mutants.
LIFE SCIENCE ALLIANCE
(2023)
Article
Chemistry, Multidisciplinary
Hiroyuki Mita, Shingo Hattori, Toshiyuki Sasaki, Satoshi Takamizawa, Kazuteru Shinozaki
Summary: We report an unprecedented result of self-aggregation of [Pt(L-1)Cl] triggered by CO2 in basic aqueous solution. The maximal degree of aggregation is at least 32-mer. The red crystals consist of Pt-Pt stacked dimer, while the blue-green crystals are constructed by linear array.
Article
Biochemistry & Molecular Biology
Xiaoqing Wang, Hao Liu, Yanfang Liu, Gefei Han, Yushu Wang, Haifeng Chen, Lin He, Gang Ma
Summary: The highly conserved hedgehog protein family plays important roles in embryonic development and tumorigenesis. This study focused on exploring the functions of the C-terminal region of the amino-terminal fragment of Indian Hedgehog (IHH-N), revealing its crucial role in signal transduction.
Article
Chemistry, Multidisciplinary
Arun Sridharan, Alexandra C. Brown, Daniel L. M. Suess
Summary: This study reports the synthesis and characterization of the first terminal imido complex of an Fe-S cluster, demonstrating competency for C-H activation. The Fe-imido site is described as a high-spin Fe3+ center, with a long Fe-N(imido) distance of 1.763(2) angstrom.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Lina Lorenzen, Dennis Frank, Carsten Schwan, Robert Grosse
Summary: FMNL2 is upregulated in several cancers and plays important roles in cell migration, invasion, cell-cell adhesion and filopodia formation. Using structured illumination microscopy, it was found that FMNL2 promotes rapid and highly dynamic filopodia formation in epithelial cells while remaining on the tip of the growing filopodia. This filopodia tip localization depends on its N-terminal myristoylation and serine 1072 phosphorylation within the diaphanous-autoregulatory domain (DAD) by protein kinase C (PKC) alpha.
Article
Neurosciences
Ellen L. Bouchard, Ana M. Meireles, William S. Talbot
Summary: (English Summary:)
Myelination by oligodendrocytes is critical for the support and survival of neurons in the central nervous system. This study reveals that TFEB, a lysosomal transcription factor, regulates oligodendrocyte differentiation and controls the length of myelin sheaths formed by individual cells.
Article
Biochemistry & Molecular Biology
Jingyan Zhang, Daniel P. Singh, Christopher Y. Ko, Roman Nikolaienko, Siobhan M. Wong King Yuen, Jacob A. Schwarz, Levy M. Treinen, Ching-Chieh Tung, Kaja Rozman, Bengt Svensson, Courtney C. Aldrich, Aleksey Zima, David D. Thomas, Donald M. Bers, Bradley S. Launikonis, Filip Van Petegem, Razvan L. Cornea
Summary: This study used NTR biosensors to screen for potential therapeutic compounds that modulate RyR channels. Several novel inhibitors and selective activators were identified, as well as a potential enhancer of excitation-contraction coupling. Additionally, further investigation of an FDA-approved antibiotic, fusidic acid, showed its ability to inhibit RyR leak but with cautionary observations of arrhythmogenic calcium transients in intact cardiomyocytes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Andrea Denardo, Stefano Elli, Stefania Federici, Michela Asperti, Magdalena Gryzik, Paola Ruzzenenti, Fernando Carmona, Paolo Bergese, Annamaria Naggi, Paolo Arosio, Maura Poli
Summary: The study demonstrates the interaction between BMP6 and heparin/HS, with N-terminal and C-terminal domains mediating this interaction. Mutations affecting heparin affinity were identified, highlighting a potential clinical approach for high-hepcidin iron disorders.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Multidisciplinary Sciences
Sabine M. Ulamec, Roberto Maya-Martinez, Emily J. Byrd, Katherine M. Dewison, Yong Xu, Leon F. Willis, Frank Sobott, George R. Heath, Patricija van Oosten Hawle, Vladimir L. Buchman, Sheena E. Radford, David J. Brockwell
Summary: In this study, the authors characterized the impact of amino acid substitution on alpha-synuclein aggregation. They found that residues 38 and 42 within the P1 region of alpha-synuclein influence amyloid formation.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Fusako Munakata, Masataka Suzawa, Kumiko Ui-Tei
Summary: Human GW182 family proteins act as scaffold proteins between AGO protein and RNA silencing-related proteins, with phosphorylation of TNRC6A affecting the interaction with the CCR4-NOT complex, which may impact RNA silencing activity.
Article
Clinical Neurology
Graciosa Q. Teixeira, Zhiyao Yong, Raquel M. Goncalves, Amelie Kuhn, Jana Riegger, Helena Brisby, Helena Barreto Henriksson, Michael Ruf, Andreas Nerlich, Uwe M. Mauer, Anita Ignatius, Rolf E. Brenner, Cornelia Neidlinger-Wilke
Summary: The study found that the deposition of terminal complement complex (TCC) positively correlated with the degree of disc degeneration. Higher CD59 positivity was found in the disc degeneration (DD) and adolescent idiopathic scoliosis (AIS) groups compared to the younger age group, and it was negatively correlated with the age of the patients.
EUROPEAN SPINE JOURNAL
(2021)
Article
Polymer Science
Naoya Kanbayashi, Manami Narukawa, Kiyotaka Onitsuka
Summary: The end-functionalization of poly(quinolylene-2,3-methylene)s (PQM) via thiocarbonylation is successfully achieved by forming an acyl palladium complex. The resulting acyl palladium complex exhibits high reactivity towards thiols, enabling the introduction of various substituents at the ω-chain end of PQM. This new end-functionalization method has the potential to be applied to other polymerization reactions using transition-metal complexes and can lead to a wide range of developments in polymer synthesis.
MACROMOLECULAR RAPID COMMUNICATIONS
(2023)
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.
Article
Biochemistry & Molecular Biology
Aleksi Sutinen, Giang Thi Tuyet Nguyen, Arne Raasakka, Gopinath Muruganandam, Remy Loris, Emil Ylikallio, Henna Tyynismaa, Luca Bartesaghi, Salla Ruskamo, Petri Kursula
Summary: This study investigates the biochemical and structural properties of GDAP1 gene mutations causing Charcot-Marie-Tooth disease. The findings reveal that these mutations lead to alterations in GDAP1 structure and decreased thermal stability, resulting in insufficient neuronal function.
Correction
Biochemistry & Molecular Biology
Giang Thi Tuyet Nguyen, Aleksi Sutinen, Arne Raasakka, Gopinath Muruganandam, Remy Loris, Petri Kursula
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Salla Ruskamo, Arne Raasakka, Jan Skov Pedersen, Anne Martel, Karel Skubnik, Tamim Darwish, Lionel Porcar, Petri Kursula
Summary: This study characterized the three-dimensional structure and functional differences of the most abundant protein in myelin, PLP, and its isoform DM20, and revealed the mechanisms of their interactions with lipids. Reconstituted PLP and DM20 spontaneously induced the formation of multi-layered membrane structures similar to myelin in the lipid bilayers. These findings contribute to a better understanding of the organization and function of proteins in compact myelin in the central nervous system.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Sigurbjorn Markusson, Erik Hallin, Helene J. Bustad, Arne Raasakka, Ju Xu, Gopinath Muruganandam, Remy Loris, Aurora Martinez, Clive R. Bramham, Petri Kursula
Summary: Activity-regulated cytoskeleton-associated protein (Arc) plays a vital role in synaptic plasticity and memory formation. This study used high-affinity anti-Arc nanobodies to investigate the structure and function of Arc. The results suggest that the N-terminal domain of Arc is involved in membrane binding, while the C-terminal domain binds to postsynaptic protein ligands. Furthermore, the NTD and CTD are important for Arc oligomerisation and assembly of capsids.
Article
Biophysics
I. S. Vaskan, A. T. Prikhodko, M. V. Petoukhov, E. V. Shtykova, N. V. Bovin, A. B. Tuzikov, V. A. Oleinikov, A. V. Zalygin
Summary: The detailed analysis of the surface structure of nanoparticles is essential for the rational design of drug delivery systems. However, characterizing the surface structure under physiological conditions is challenging. In this study, the combination of SAXS contrast variation and ab initio bead modeling was used to investigate nanoparticle surface structure. By gradually increasing the solvent electron density, the shell coating thickness and uniformity around the nanoparticle core were assessed.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
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
Multidisciplinary Sciences
Aleksi Sutinen, Dirk Paffenholz, Giang Thi Tuyet Nguyen, Salla Ruskamo, Andrew E. Torda, Petri Kursula
Summary: Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral polyneuropathy in humans, and its subtypes are linked to mutations in dozens of different genes, including the gene coding for ganglioside-induced differentiation-associated protein 1 (GDAP1). The etiology of GDAP1-linked CMT is poorly understood at the protein level, despite implications for mitochondrial fission and fusion, cytoskeletal interactions, and response to reactive oxygen species. Structural and biophysical analyses on several CMT-linked GDAP1 protein variants have been carried out, and new crystal structures of these variants have been described.
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
Biochemistry & Molecular Biology
Dorothee Houry, Arne Raasakka, Eugenio Ferrario, Marc Niere, Ersilia Bifulco, Petri Kursula, Mathias Ziegler
Summary: In this study, the mechanism of increased substrate affinity of phosphorylated NAMPT is revealed, which includes the coordination of Mg2+ by phospho-His247 to stabilize PRPP in a position favorable for catalysis. Additionally, a stretch of 10 amino acids found only in NAMPTs from deuterostomes is shown to enhance conformational plasticity and stabilize the chemically unstable phosphorylation of His247. Overall, this study provides a structural basis for the important function of NAMPT in recycling Nicotinamide into NAD biosynthesis with high affinity.
JOURNAL OF STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Oda C. Krokengen, Arne Raasakka, Petri Kursula
Summary: Numerous human proteins, known as intrinsically disordered proteins (IDPs), lack high-resolution structural information due to their physicochemical properties. However, IDPs can adopt local ordered structures upon interaction with other proteins or lipid membranes. Using AlphaFold2 predictions and experimental data, we have found that the predicted models of two myelin-specific IDPs closely match their membrane-binding sites. These artificial intelligence-based models provide insight into the ligand-bound state of IDPs and are crucial for understanding the role of IDPs in diseases.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Alexander L. L. Ksenofontov, Maxim V. V. Petoukhov, Vladimir V. V. Matveev, Natalia V. V. Fedorova, Pavel I. I. Semenyuk, Alexander M. M. Arutyunyan, Tatiana I. I. Manukhova, Ekaterina A. A. Evtushenko, Nikolai A. A. Nikitin, Olga K. V. Karpova, Eleonora V. V. Shtykova
Summary: The amino acid sequences of the coat proteins (CPs) of PVX and AltMV share about 40% identity. The N-terminal domains of these proteins differ in sequence and the presence of an N-terminal fragment in PVX CP. The N-terminal domain of PVX CP contributes to the higher thermal stability and ordered structure of PVX virions compared to AltMV.
BIOCHEMISTRY-MOSCOW
(2023)