Review
Chemistry, Multidisciplinary
Fengbin Wang, Ordy Gnewou, Armin Solemanifar, Vincent P. Conticello, Edward H. Egelman
Summary: Cryo-EM is the preferred method for structural analysis of synthetic helical filaments, and it has revealed the enormous potential for polymorphism in self-assembled soft matter polymers. These structures have also highlighted the chaotic self-assembly behavior that makes it difficult to predict the structure of these polymers.
Article
Multidisciplinary Sciences
Abhimanyu K. Singh, Brent De Wijngaert, Marc Bijnens, Kris Uyttersprot, Hoai Nguyen, Sergio E. Martinez, Dominique Schols, Piet Herdewijn, Christophe Pannecouque, Eddy Arnold, Kalyan Das
Summary: A protocol for rapid structure determination of HIV-1 reverse transcriptase (RT) complexes by cryo-electron microscopy (cryo-EM) has been optimized. Six structures of RT complexes with nonnucleoside inhibitors were determined, revealing important differences in structure and conformation. These differences have implications for understanding drug resistance mechanisms and drug design.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Elena Farah Lehmann, Marton Liziczai, Katarzyna Drozdzyk, Patrick Altermatt, Cassiano Langini, Vania Manolova, Hanna Sundstrom, Franz Durrenberger, Raimund Dutzler, Cristina Manatschal
Summary: The regulatory mechanism of iron homeostasis in humans involves the interaction between ferroportin (FPN) and hepcidin, and dysregulation leads to various pathological conditions. Vamifeport, a clinical-stage FPN inhibitor, competes with hepcidin for FPN binding. Cryo-electron microscopy structures reveal the conformational changes of FPN and the binding site of Vamifeport. This study provides insights into the structural and pharmacological aspects of FPN.
Article
Multidisciplinary Sciences
Filipe Nunes Vicente, Mickael Lelek, Jean-Yves Tinevez, Quang D. Tran, Gerard Pehau-Arnaudet, Christophe Zimmer, Sandrine Etienne-Manneville, Gregory Giannone, Cecile Leduc
Summary: Intermediate filaments play key roles in cellular functions and their mechanical properties. This study used super-resolution microscopy to reveal the molecular organization of vimentin filaments and provided evidence for the partial overlap of subunits during filament assembly. The researchers also found that the extensibility of vimentin is due to the unfolding of its subunits, establishing a direct link between structure and mechanics.
Review
Biochemistry & Molecular Biology
Zuoneng Wang, Qingyang Zhang, Carsten Mim
Summary: Cryo electron microscopy has become the most important method in structural biology, with single particle analysis and electron tomography being the main approaches, while sub-tomogram averaging has matured. Current resolution ranges from 2 to 5 angstrom, showing promise for future developments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Jin-Hu Dou, Maxx Q. Arguilla, Yi Luo, Jian Li, Weizhe Zhang, Lei Sun, Jenna L. Mancuso, Luming Yang, Tianyang Chen, Lucas R. Parent, Grigorii Skorupskii, Nicole J. Libretto, Chenyue Sun, Min Chieh Yang, Phat Vinh Dip, Edward J. Brignole, Jeffrey T. Miller, Jing Kong, Christopher H. Hendon, Junliang Sun, Mircea Dinca
Summary: Researchers have successfully grown single crystals of 2D metal-organic frameworks up to 200 µm in size by balancing in-plane and out-of-plane interactions, revealing anisotropic transport and a clear correlation between conductivity and the nature of the metal cation in the sheets.
Article
Neurosciences
Yang Yang, Alexey G. Murzin, Sew Peak-Chew, Catarina Franco, Holly J. Garringer, Kathy L. Newell, Bernardino Ghetti, Michel Goedert, Sjors H. W. Scheres
Summary: In this study, the structures of A beta 40 filaments in individuals with Alzheimer's disease and cerebral amyloid angiopathy were determined using electron cryo-microscopy. The findings revealed differences in the sequence assignment and interactions of A beta 40 peptides, redefining their fold. Additionally, distinct structures were observed between parenchymal deposits of A beta 42 and blood vessel deposits of A beta 40, supporting the idea that Alzheimer's disease and cerebral amyloid angiopathy are different A beta proteinopathies.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Marie-Luise Frey, Shen Han, Henry Halim, Anke Kaltbeitzel, Andreas Riedinger, Katharina Landfester, Ingo Lieberwirth
Summary: This study analyzes the intracellular fate of protein-based nanocarriers along their endolysosomal pathway using correlative light and electron microscopy methods. It identifies different cell compartments involved in the processing of nanocarriers and presents three different terminal routes for their intracellular destiny. These findings contribute to the understanding of the degradation process of protein nanocapsules and the therapeutic success of encapsulated drugs.
Article
Biochemistry & Molecular Biology
William Lehman, Elumalai Pavadai, Michael J. Rynkiewicz
Summary: TnI interacts with tropomyosin to induce muscle relaxation under low-Ca2+ conditions and releases inhibition under high-Ca2+ conditions. Recent cryo-EM reconstructions have shown density attributed to TnI along cardiac muscle thin filaments at both low- and high-Ca2+ concentration.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Cell Biology
Jocelyn F. Krey, Chang Liu, Inna A. Belyantseva, Michael Bateschell, Rachel A. Dumont, Jennifer Goldsmith, Paroma Chatterjee, Rachel S. Morrill, Lev M. Fedorov, Sarah Foster, Jinkyung Kim, Alfred L. Nuttall, Sherri M. Jones, Dongseok Choi, Thomas B. Friedman, Anthony J. Ricci, Bo Zhao, Peter G. Barr-Gillespie
Summary: The stereocilia rootlet plays a critical role in protecting vertebrate hair cells from overstimulation. This study demonstrates that the ANKRD24 protein concentrates at the insertion point of the stereocilia, forming a ring and binding with TRIOBP-5 to maintain its distribution. ANKRD24 and TRIOBP-5 together organize the rootlets, enabling long-term auditory resilience.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Luigi Parrotta, Lavinia Mareri, Iris Aloisi, Claudia Faleri, Gaetano Distefano, Alessandra Gentile, Angela Roberta Lo Piero, Verena Kriechbaumer, Marco Caruso, Giampiero Cai, Stefano Del Duca
Summary: This study investigated the effects of clementine ASP-RICH proteins on pollen tubes by expressing them in tobacco. The results showed that ASP-RICH modulated Ca2+ content, which in turn affected cytoskeleton organization and cell wall deposition, ultimately impacting the growth pattern of pollen tubes. These findings suggest a regulatory role of ASP-RICH in the mechanism of plant cell growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Jiro Usukura, Akihiro Narita, Tomoharu Matsumoto, Eiji Usukura, Takeshi Sunaoshi, Syunya Watanabe, Yusuke Tamba, Yasuhira Nagakubo, Takashi Mizuo, Junzo Azuma, Masako Osumi, Kazutaka Nimura, Ryuichiro Tamochi, Yoichi Ose
Summary: The new type of cryo-electron microscope allows simultaneous acquisition of transmission and surface images, with high-quality images at 30 kV. Using the unroofing method, fine structures near the cell membrane become visible, including the cytoskeleton, polyribosome chains, and endoplasmic reticulum.
SCIENTIFIC REPORTS
(2021)
Review
Physiology
Michael J. Rynkiewicz, Elumalai Pavadai, William Lehman
Summary: This article investigates the mechanism of calcium-dependent regulation of striated muscle contraction and reveals key intermolecular interactions and conformational changes through modeling and molecular dynamics simulation. It is of great significance for understanding mutation-induced contractile dysfunction related to muscle diseases.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biology
Jeong Min Chung, Osamu Sato, Reiko Ikebe, Sangmin Lee, Mitsuo Ikebe, Hyun Suk Jung
Summary: This study investigated the mechanism by which fascin-1 induces actin bundling and its localization along actin filaments. The researchers found that the N-terminal region of fascin-1 is responsible for actin bundling, while the C-terminal region is important for fascin-1 dimerization. Furthermore, they discovered that the intermolecular interactions of the C-terminal region are essential for actin bundling.
Article
Multidisciplinary Sciences
Steven Z. Chou, Moon Chatterjee, Thomas D. Pollard
Summary: By analyzing the images collected by electron cryo-microscopy, we reconstructed the structure of actin filament branch junctions formed by fission yeast Arp2/3 complex. The formation of this structure requires a conformational change of the Arp2/3 complex and the acquisition of a new buried surface area to maintain the stability of the branch.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Bjoern U. Klink, Eric Herrmann, Claudia Antoni, Lars Langemeyer, Stephan Kiontke, Christos Gatsogiannis, Christian Ungermann, Stefan Raunser, Daniel Kuemmel
Summary: This study presents a high-resolution cryogenic electron microscopy structure of the Mon1-Ccz1 complex, revealing its strong scaffold for the catalytic center and the phosphatidylinositol phosphate-binding site, providing molecular insights into endosomal Rab activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Zhexin Wang, Michael Grange, Sabrina Pospich, Thorsten Wagner, Ay Lin Kho, Mathias Gautel, Stefan Raunser
Summary: This study reveals the structure of nebulin bound to thin filaments and demonstrates its stabilizing role. It also highlights the different interactions of nebulin with actin and myosin, as well as its interaction with a troponin T linker, explaining its regulatory function.
Article
Biochemistry & Molecular Biology
Tobias Raisch, Giuseppe Ciossani, Ennio D'Amico, Verena Cmentowski, Sara Carmignani, Stefano Maffini, Felipe Merino, Sabine Wohlgemuth, Ingrid R. Vetter, Stefan Raunser, Andrea Musacchio
Summary: A high-resolution cryo-EM structure of the ROD-Zwilch-ZW10 complex reveals essential features, such as a farnesyl-binding site required for Spindly binding. In vitro assays demonstrate that the SAC kinase MPS1 is necessary and sufficient for corona assembly at supercritical concentrations of the RZZ-Spindly complex, and the molecular mechanism of phosphorylation-dependent filament nucleation is described.
Article
Multidisciplinary Sciences
Alexander Belyy, Florian Lindemann, Daniel Roderer, Johanna Funk, Benjamin Bardiaux, Jonas Protze, Peter Bieling, Hartmut Oschkinat, Stefan Raunser
Summary: This study reveals in atomic detail how the TccC3 enzyme modifies actin and disrupts the cellular cytoskeleton. The binding of TccC3 to F-actin occurs through an induced-fit mechanism, leading to the transfer of ADP-ribose to a specific site on F-actin. This site-specific modification prevents the interaction of F-actin with depolymerization factors, impairing actin network turnover and promoting steady actin polymerization.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Florian Kuellmer, Nynke A. Veprek, Malgorzata Borowiak, Veselin Nasufovic, Sebastian Barutzki, Oliver Thorn-Seshold, Hans-Dieter Arndt, Dirk Trauner
Summary: We have developed a new generation of photoswitchable jasplakinolides that can be activated with visible light and rapidly return to an inactive state through thermal relaxation. This reversible control of F-actin dynamics has been demonstrated in live-cell imaging, cell migration, and cell proliferation assays. Our optical tool offers excellent spatiotemporal resolution and can be useful in various fields.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Wout Oosterheert, Bjorn U. Klink, Alexander Belyy, Sabrina Pospich, Stefan Raunser
Summary: The structures of F-actin in different nucleotide states were determined using cryo-electron microscopy, revealing the role of water molecules and their impact on polymerization rates. These findings provide important insights into the assembly and aging mechanisms of F-actin filaments, as well as the design of drugs and small molecules for imaging and therapeutic applications.
Article
Multidisciplinary Sciences
Ying Xu, Raghuvir Viswanatha, Oleg Sitsel, Daniel Roderer, Haifang Zhao, Christopher Ashwood, Cecilia Voelcker, Songhai Tian, Stefan Raunser, Norbert Perrimon, Min Dong
Summary: This study identifies Visgun (Vsg) as a protein receptor for a Photorhabdus luminescens toxin complex (Tc) toxin. The toxin recognizes a specific domain of Vsg and forms a complex with it. Knocking out Vsg in fruit flies increases resistance to P. luminescens infection. These findings contribute to our understanding of the specificity and pathogenesis of Tc toxins.
Article
Biochemical Research Methods
Gavin Rice, Thorsten Wagner, Markus Stabrin, Oleg Sitsel, Daniel Prumbaum, Stefan Raunser
Summary: TomoTwin is a deep metric learning-based particle picking method for cryo-electron tomograms that eliminates the need for annotating training data and retraining a picking model for each protein. It embeds tomograms in a high-dimensional space to identify proteins without manual annotation or network retraining.
Review
Biochemistry & Molecular Biology
Tobias Raisch, Stefan Raunser
Summary: Insecticides play a crucial role in plant protection in modern agriculture. Despite their structural heterogeneity, many neurotoxic insecticides share similar principles for inhibiting or deregulating neuronal ion channels. To combat resistance and target specific pests, researchers have characterized insecticide targets and proposed structure-based development of insecticides.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Wout Oosterheert, Florian E. C. Blanc, Ankit Roy, Alexander Belyy, Micaela Boiero Sanders, Oliver Hofnagel, Gerhard Hummer, Peter Bieling, Stefan Raunser
Summary: This study reveals the mechanism of inorganic phosphate (Pi) release from actin through a 'molecular backdoor' by combining cryo-EM, molecular-dynamics simulations, and in vitro reconstitution. The backdoor opens transiently through amino acid rearrangements, explaining the rapid release of Pi from the filament end and slow release from internal subunits. The study also finds that a disease-linked actin variant distorts the backdoor arrangement, resulting in accelerated Pi release.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Organic
Florian Kuellmer, Lucas Gregor, Hans-Dieter Arndt
Summary: In this study, a variety of asymmetric azobenzenes were synthesized and characterized by addressing selected structural features of the diazene core. The systematic exploration led to the development of photoswitches with different relaxation half-lives and the influence of different substitution patterns on the photophysical properties was investigated. Furthermore, robust characterization and examination under near-to physiological conditions were performed to assist with the selection of photoswitches for specific biological applications.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
