Review
Pharmacology & Pharmacy
Christian Dahlstroem, Themistoklis Paraschiakos, Han Sun, Sabine Windhorst
Summary: Cellular actin dynamics is regulated by various actin binding proteins (ABPs), including nucleating, bundling, cross-linking, capping, and severing proteins. This review focuses on the regulation of actin dynamics by ABPs, with a specific emphasis on the role of cofilin-1, an F-actin severing protein, and L-plastin, an F-actin bundling protein. As the up-regulation of these proteins in cancer is associated with malignant progression, the cryo-EM structure of F-actin with the respective ABP could be used as a template for in silico drug design to disrupt their interaction.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biology
Daan Vorselen, Sarah R. Barger, Yifan Wang, Wei Cai, Julie A. Theriot, Nils C. Gauthier, Mira Krendel
Summary: The study reveals that during macrophage phagocytosis of antibody-opsonized targets, there is a prominent constriction driven by Arp2/3-mediated assembly of discrete actin protrusions. Contractile myosin-II activity contributes to late-stage phagocytic force generation and target ingestion. Observations of partial target eating attempts and sudden target release suggest that constriction may play a critical role in resolving complex in vivo target encounters.
Article
Multidisciplinary Sciences
Lin Mei, Matthew J. Reynolds, Damien Garbett, Rui Gong, Tobias Meyer, Gregory M. Alushin
Summary: This study focuses on the role of T-plastin in constructing actin networks. By using a machine-learning-enabled cryo-electron microscopy technique, the researchers uncover a sequential bundling mechanism that allows T-plastin to bridge and link parallel and antiparallel actin filaments. This bridging mechanism is essential for adapting to different actin network structures and functions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Amandeep S. Arora, Hsiang-Ling Huang, Ramanpreet Singh, Yoshie Narui, Andrejus Suchenko, Tomoyuki Hatano, Sarah M. Heissler, Mohan K. Balasubramanian, Krishna Chinthalapudi, Pekka Lappalainen
Summary: The structures of actin isoforms have been determined at high resolution, revealing their specific conformations and isoform-specific interfaces. These findings provide important insights into the function of actin isoforms and contribute to our overall understanding of cytoskeletal physiology.
Article
Cell Biology
Xinyu Liu, Pin Huan, Baozhong Liu
Summary: This study reveals the crucial role of nonmuscle myosin II (NM II) in the morphogenesis of the larval shell field in L. goshimai. Inhibition of NM II phosphorylation results in the complete loss of the larval shell plate and altered morphology and cell specification in the shell field.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Bojian Ding, Heidy Y. Narvaez-Ortiz, Yuvraj Singh, Glen M. Hocky, Saikat Chowdhury, Brad J. Nolen
Summary: Arp2/3 complex nucleates branched actin filaments and provides pushing forces for cellular processes. This study reveals the contacts between Arp2/3 complex and the mother actin filament, suggesting that actin filaments stimulate subunit flattening for complex activation. However, limited contact between the bottom half of the complex and the mother filament may explain why actin filaments are required but insufficient to trigger nucleation during WASP-mediated activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Yolla German, Loan Vulliard, Anton Kamnev, Laurene Pfajfer, Jakob Huemer, Anna-Katharina Mautner, Aude Rubio, Artem Kalinichenko, Kaan Boztug, Audrey Ferrand, Joerg Menche, Loic Dupre
Summary: The immunological synapse decodes stimulatory signals into adapted lymphocyte responses, and high-content imaging is used to analyze T and NK cells. The study demonstrates how actin cytoskeleton remodeling shapes synapse architecture and affects lytic granule positioning. Analysis of immunodeficient individuals' CD8(+) T cells reveals the roles of ARPC1B and WASP in synapse assembly.
Review
Biochemistry & Molecular Biology
Zhexin Wang, Stefan Raunser
Summary: Muscles are critical for movement and heart function, and their contractions rely on the sliding of thin and thick filaments. Various proteins, including actin, tropomyosin, and troponin, are involved in the contraction mechanism, and their dysfunctions can lead to muscle diseases. Recent high-resolution structural data and advancements in cryo-electron microscopy have greatly improved our understanding of the molecular details of muscle proteins and their interactions, shedding light on new avenues of muscle research.
ANNUAL REVIEW OF BIOCHEMISTRY
(2023)
Article
Cell Biology
Allison M. Gabbert, Joseph P. Campanale, James A. Mondo, Noah P. Mitchell, Adele Myers, Sebastian J. Streichan, Nina Miolane, Denise J. Montell
Summary: This study reveals the requirements for septins in the detachment and motility of border cell clusters in the Drosophila ovary. Septins and myosin colocalize dynamically at the cluster periphery and share phenotypes but do not impact each other. Instead, Rho independently regulates myosin activity and septin localization. Mathematical analyses identify that manipulating septin expression level alters cluster surface texture and shape.
DEVELOPMENTAL CELL
(2023)
Article
Cell Biology
Wencan Ke, Bingjin Wang, Wenbin Hua, Yu Song, Saideng Lu, Rongjin Luo, Gaocai Li, Kun Wang, Zhiwei Liao, Qian Xiang, Shuai Li, Xinghuo Wu, Yukun Zhang, Cao Yang
Summary: The study found that compression stress increased the interaction between myosin IIA and actin, while decreasing the interaction between myosin IIB and actin. Remodeling of the actomyosin cytoskeleton was involved in the fibrotic phenotype induced by compression stress, mediated by MRTF-A nuclear translocation and proliferation inhibition in NP cells. Activation of the RhoA/ROCK1 pathway mediated compression stress-induced senescence in human NP cells by regulating the interaction between myosin IIA and IIB with actin.
CELL PROLIFERATION
(2021)
Article
Chemistry, Physical
David P. Klebl, Robert W. Kay, Frank Sobott, Nikil Kapur, Stephen P. Muench
Summary: Sample preparation is a significant problem in single particle cryo-EM workflows, and our understanding and developments in this area are lagging behind image processing and microscope design. Recent evidence suggests that many problems occur during sample preparation within the thin film created during the conventional blotting process. Faster grid preparation methods have been developed for time-resolved cryo-EM experiments, but they still face challenges as interactions with the air-water interface cannot be avoided.
FARADAY DISCUSSIONS
(2022)
Article
Multidisciplinary Sciences
Anjie Xia, Xihao Yong, Changbin Zhang, Guifeng Lin, Guowen Jia, Chang Zhao, Xin Wang, Yize Hao, Yifei Wang, Pei Zhou, Xin Yang, Yue Deng, Chao Wu, Yujiao Chen, Jiawei Zhu, Xiaodi Tang, Jingming Liu, Shiyu Zhang, Jiahao Zhang, Zheng Xu, Qian Hu, Jinlong Zhao, Yuting Yue, Wei Yan, Zhaoming Su, Yuquan Wei, Rongbin Zhou, Haohao Dong, Zhenhua Shao, Shengyong Yang
Summary: This study presents the cryo-EM structures of GPR34 bound with LysoPS and its inhibition by the antagonist YL-365. The findings provide mechanistic insights into the endogenous agonist recognition and antagonist inhibition of GPR34, highlighting GPR34 as a promising target for disease treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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
Xiao Fan, Jian Huang, Xueqin Jin, Nieng Yan
Summary: Voltage-gated sodium channel Nav1.6 is crucial for neuronal firing and its dysfunction can lead to epilepsy and neurological disorders. The cryo-EM structure of human Nav1.6 reveals its inactivated state with closed pore domain and all up voltage-sensing domains. The presence of an unidentified molecule bound to the Nav1.6 PD suggests a potential target for developing specific blockers.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Dan-Dan Chen, Jia Hao, Chao-Hui Shen, Xian-Ming Deng, Cai-Hong Yun
Summary: The PA28 family proteasome activators play crucial roles in regulating proteasome activities. However, the paralogs, PA28 alpha, PA28 beta, and PA28 gamma, have distinct expression patterns, cellular localizations, and biological functions. This study provides an atomic resolution Cryo-EM structure of the human PA28 gamma heptamer, revealing unique structural features that may contribute to our understanding of its functional mechanisms.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Chemistry, Multidisciplinary
Sabrina Pospich, Florian Kuellmer, Veselin Nasufovic, Johanna Funk, Alexander Belyy, Peter Bieling, Hans-Dieter Arndt, Stefan Raunser
Summary: This study presents the structures of a cell-permeable optojasp bound to actin filaments and highlights the effects of photoswitching a functionalized azobenzene for the first time. Analyzing the binding site and conformational changes within F-actin dependent on the optojasp isomeric state refines the determinants for designing functional F-actin photoswitches.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Zhexin Wang, Michael Grange, Thorsten Wagner, Ay Lin Kho, Mathias Gautel, Stefan Raunser
Summary: Through electron cryo-tomography, we revealed the molecular architecture of vertebrate skeletal sarcomeres, including the organization and interaction of actin and myosin in the A-band, I-band, and Z-disc, as well as the cross-linking mechanism of alpha-actinin. Additionally, our study identified two conformations of double-head myosin, shedding light on its interaction with actin filaments and splitting between them.
Article
Multidisciplinary Sciences
Julien Robert-Paganin, Xiao-Ping Xu, Mark F. Swift, Daniel Auguin, James P. Robblee, Hailong Lu, Patricia M. Fagnant, Elena B. Krementsova, Kathleen M. Trybus, Anne Houdusse, Niels Volkmann, Dorit Hanein
Summary: This study presents the atomic structure of the Plasmodium falciparum actomyosin system and reveals the detailed interactions required for producing the force and motion during infectivity. Despite significant differences in the myosin and actin elements, the footprint of the myosin motor on filamentous actin remains conserved compared to higher eukaryotes.
NATURE COMMUNICATIONS
(2021)
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
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
Multidisciplinary Sciences
Louise Canon, Carlos Kikuti, Vicente J. Planelles-Herrero, Tianming Lin, Franck Mayeux, Helena Sirkia, Young il Lee, Leila Heidsieck, Leonid Velikovsky, Amandine David, Xiaoyan Liu, Dihia Moussaoui, Emma Forest, Peter Hook, Karl J. Petersen, Tomos E. Morgan, Aurelie Di Cicco, Julia Sires-Campos, Emmanuel Derivery, Daniel Levy, Cedric Delevoye, H. Lee Sweeney, Anne Houdusse
Summary: Canon et al. provide insights into the auto-inhibition and activation of the minus-end directed motor myosin VI. The study highlights how differential relief of auto-inhibition allows for fine control of myosin VI activity in vivo.
NATURE COMMUNICATIONS
(2023)
