Article
Microbiology
Andrea Lopez, Maria Andreadaki, Juha B. Vahokoski, Elena Deligianni, Lesley Calder, Serena Camerini, Anika K. Freitag, Ulrich Bergmann, Peter K. Rosenthal, Inga Siden-Kiamos, Inari K. Kursula
Summary: Actin I and Actin II in malaria parasites have different structures and functions, with Actin I playing a key role in motility and Actin II being involved in male gametogenesis and the oocyst stage. Actin II readily forms long filaments in vitro and has similar structures to Actin I. Mutational analysis reveals that long and stable filaments are necessary for male gametogenesis, and fine-tuned regulation by methylation of histidine 73 is required for the second function in the oocyst stage. Actin II polymerizes via the nucleation-elongation mechanism, and dimers are a stable form at equilibrium.
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
Biochemistry & Molecular Biology
Meinan Lyu, Chih-Chia Su, James W. Kazura, Edward W. Yu
Summary: The intra-erythrocyte stage of P. falciparum relies on glycolysis to generate energy, with potential toxicity from lactic acid as a metabolic byproduct. The membrane protein PfFNT acts as a transporter for lactate, providing a mechanism for exporting these acids from the parasite.
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
Julea Vlassakis, Louise L. Hansen, Ryo Higuchi-Sanabria, Yun Zhou, C. Kimberly Tsui, Andrew Dillin, Haiyan Huang, Amy E. Herr
Summary: This research introduces a novel method to simultaneously detect protein complexes in stressed cell populations, revealing potential cellular responses to specific treatments. The study also highlights the impact of non-chemical stress on cellular heterogeneity of F-actin. The assay developed in this work overcomes selectivity limitations to biochemically quantify single-cell protein complexes perturbed with diverse stimuli.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Wim J. H. Hagen
Summary: Researchers have presented an energy filter-based plasmon imaging method for rapid screening of gold foil grids, in order to save expensive imaging time.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biology
Erumbi S. S. Rangarajan, Emmanuel W. W. Smith, Tina Izard
Summary: Cell attachment is crucial and mediated by cadherin receptors binding and alpha-catenin interaction. Alpha-catenin modulates cell migration and adhesion by linking junctions and plasma membrane to actin cytoskeleton. CryoEM structures provide mechanistic insights into alpha-catenin function and its role in cell adhesion and disease.
COMMUNICATIONS BIOLOGY
(2023)
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
Tommi Kotila, Hugo Wioland, Muniyandi Selvaraj, Konstantin Kogan, Lina Antenucci, Antoine Jegou, Juha T. Huiskonen, Guillaume Romet-Lemonne, Pekka Lappalainen
Summary: The authors report the structure and function analysis of highly divergent actin from Leishmania parasite. The study reveals the rapid dynamics and molecular basis of parasite actin, providing insight into the evolution of the actin cytoskeleton. The findings show how divergent parasites achieve rapid actin dynamics using a simple set of actin-binding proteins, elucidating the evolution of the actin cytoskeleton.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Domen Kampjut, Julia Steiner, Leonid A. Sazanov
Summary: Our study systematically investigated the effects of buffer components, blotting conditions, and grid types on membrane protein grid preparation. We found that aggregation was a common issue, which could be addressed by adjusting detergents, salt concentration, or reconstitution methods. Furthermore, we discussed strategies for achieving optimal ice thickness, particle coverage, and orientation distribution on both free ice and support films. Our findings provide a clear roadmap for comprehensive screening of conditions for cryo-EM grid preparation of membrane proteins.
Article
Medicine, General & Internal
Melissa D. Conrad, Victor Asua, Shreeya Garg, David Giesbrecht, Karamoko Niare, Sawyer Smith, Jane F. Namuganga, Thomas Katairo, Jennifer Legac, Rebecca M. Crudale, Patrick K. Tumwebaze, Samuel L. Nsobya, Roland A. Cooper, Moses R. Kamya, Grant Dorsey, Jeffrey A. Bailey, Philip J. Rosenthal
Summary: This study identified multifocal emergence and spread of Plasmodium falciparum with partial resistance to artemisinins in Uganda. The emergence and spread of resistance were predominantly observed in areas where effective malaria control had been discontinued or transmission was unstable.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Biology
Fumiya K. Sano, Hiroaki Akasaka, Wataru Shihoya, Osamu Nureki, David Drew
Summary: This study reports the structure of the complex between the endothelin ETB receptor and G-protein, revealing how endothelin activates the ETB receptor and expanding the diversity of G-protein binding modes.
Article
Multidisciplinary Sciences
Qi Jia, Ye Xiang
Summary: In this study, the cryo-EM structure of a M13 mini variant bacteriophage was reported. The mini phage has two cap-like complexes at its distal ends, formed by minor coat proteins. The inner single stranded DNA genome adopts a helical structure similar to double-stranded DNA.
NATURE COMMUNICATIONS
(2023)
Article
Parasitology
Linda E. Amoah, Kwame K. Asare, Donu Dickson, Sherik-Fa Anang, Abena Busayo, Dorcas Bredu, George Asumah, Nana Peprah, Alexander Asamoah, Benjamin Abuaku, Keziah L. Malm
Summary: Clinical presentations of malaria in Ghana are mainly caused by Plasmodium falciparum, with a minor contribution from Plasmodium malariae and Plasmodium ovale. PCR can detect low-density (submicroscopic) malaria infections, and more sensitive point-of-care tools are needed to diagnose these cases.
PARASITES & VECTORS
(2022)
Article
Multidisciplinary Sciences
Shanshan Li, Michael Z. Palo, Grigore Pintilie, Xiaojing Zhang, Zhaoming Su, Kalli Kappel, Wah Chiu, Kaiming Zhang, Rhiju Das
Summary: The Tetrahymena group I intron has provided valuable insights into the folding and misfolding of RNA. In this study, cryo-EM was used to visualize the misfolded structures of the Tetrahymena L-21 ScaI ribozyme. Multiple misfolded substates were identified and compared to the native state, revealing topological differences that explain the failure of substrate docking and suggest pathways for refolding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Abris Adam Bendes, Petri Kursula, Inari Kursula
Summary: Apicomplexan parasites rely on the glideosome for motility and host cell invasion; actin filament capping proteins (CPs) play a crucial role in regulating actin dynamics; this study presents the crystal structure of CP from the malaria parasite and reveals differences compared to canonical heterodimers.
CELLULAR AND MOLECULAR LIFE SCIENCES
(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
Microbiology
Juha Vahokoski, Lesley J. Calder, Andrea J. Lopez, Justin E. Molloy, Inari Kursula, Peter B. Rosenthal
Summary: In this study, the structure of the malaria parasite motor complex was presented, including the actin 1 and myosin A with its associated light chains. Malaria is a deadly disease that causes significant mortality and economic burden globally, and the parasite responsible for the disease relies on the actomyosin motor complex for its motility and invasion. Understanding the structure of this complex provides insights for drug development targeting this complex.
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
Biochemistry & Molecular Biology
Isa Pires, Yu-Fu Hung, Ulrich Bergmann, Justin E. Molloy, Inari Kursula
Summary: MyoB, a myosin expressed in the invasive stages of Plasmodium falciparum, contributes to red blood cell invasion. It binds to actin and multiple regulatory light chains, exhibits ATPase activity, and moves actin filaments. Its specific localization, high affinity to actin, and ability to sense and apply force may be important for early stages of invasion.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Laura Giorgi, Akseli Niemela, Esa-Pekka Kumpula, Ossi Natri, Petteri Parkkila, Juha T. Huiskonen, Artturi Koivuniemi
Summary: This study combines coarse-grained molecular dynamics simulations with complementary experiments to gain mechanistic insight into how apoA-I mimetic peptide 22A and its variants tune LCAT activity in peptide-lipid nanodiscs. Results show that peptide 22A forms transient antiparallel dimers at the rim of nanodiscs, and the removal of C-terminal lysine K22 decreases dimerization tendency and LCAT activity. Furthermore, simulations reveal that LCAT localizes preferentially to the rim of nanodiscs in a manner that shields important domains from water phase, and the conformation of LCAT in the rim affects its activity.
MOLECULAR PHARMACEUTICS
(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
Cell Biology
Vera Kovaleva, Li-Ying Yu, Larisa Ivanova, Olesya Shpironok, Jinhan Nam, Ave Eesmaa, Esa-Pekka Kumpula, Sven Sakson, Urve Toots, Mart Ustav, Juha T. Huiskonen, Merja H. Voutilainen, Paivi Lindholm, Mati Karelson, Mart Saarma
Summary: MANF is a protein located in the ER, shown to have cytoprotective effects in neurons and pancreatic b cells. This study demonstrates that MANF directly interacts with IRE1a, an ER transmembrane protein, and attenuates UPR signaling and protects neurons from ER stress-induced death. The interaction between MANF and IRE1a, but not MANF-BiP interaction, is crucial for MANF's pro-survival activity.
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)