Article
Chemistry, Multidisciplinary
Chao Wang, Bidong Zhang, Arne Kruger, Xiaochen Du, Lidia Visser, Alexander S. S. Domling, Carsten Wrenger, Matthew R. Groves
Summary: This study describes a series of small-molecule inhibitors targeting P. falciparum ATC with low nanomolar binding affinities, selectively binding to a previously unreported allosteric pocket, inhibiting ATC activation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Anna Turkiewicz, Emilia Manko, Damiola R. Oresegun, Debbie Nolder, Anton Spadar, Colin J. Sutherland, Janet Cox-Singh, Robert W. Moon, Yee-Ling Lau, Susana Campino, Taane G. Clark
Summary: The genetic diversity of the zoonotic Plasmodium knowlesi parasite in Southeast Asia has important implications for its evolution, diagnostics, transmission dynamics, and drug resistance. Previous studies have identified three sub-populations of P. knowlesi based on geographical location and macaque host. However, the genetic structure of non-Borneo sub-populations is still unclear. By analyzing a large collection of P. knowlesi whole-genome sequencing data, this study reveals genetic exchange events and differences in different clusters linked to mosquito-related stages and host-related stages.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Vanndita Bahl, Kritika Chaddha, Syed Yusuf Mian, Anthony A. Holder, Ellen Knuepfer, Deepak Gaur
Summary: The novel protein PfMSA180 plays an essential role in parasite egress in Plasmodium falciparum, highlighting its potential as a target for novel malaria intervention strategies.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Ralf Kleene, Gabriele Loers, Gaston Castillo, Melitta Schachner
Summary: Cell adhesion molecule L1 regulates multiple cell functions and its deficiency is linked to neural diseases. The interaction between L1 and HP1 isoforms affects L1-dependent functions, such as neurite outgrowth and neuronal migration.
Article
Cell Biology
Gyuri Sim, Moonkyung Jeong, Hyunseok Seo, Jangrae Kim, Soojin Lee
Summary: Neuronal growth regulator 1 (NEGR1) is involved in neural cell communication and synapse formation, and its N-glycan residues play important roles in the folding, trafficking, and homodimer formation of NEGR1 protein.
Article
Microbiology
Stephen W. Scally, Tony Triglia, Cindy Evelyn, Benjamin A. Seager, Michal Pasternak, Pailene S. Lim, Julie Healer, Niall D. Geoghegan, Amy Adair, Wai-Hong Tham, Laura F. Dagley, Kelly L. Rogers, Alan F. Cowman
Summary: This study identified the importance of the PCRCR complex, consisting of PfPTRAMP and PfCSS, in the invasion of erythrocytes by Plasmodium falciparum. The PCRCR complex plays a role in anchoring the contact between merozoite and erythrocyte membranes, facilitated by strong parasite deformations. In addition, the study identified inhibitory epitopes, which can guide the development of a malaria vaccine targeting the blood stage.
NATURE MICROBIOLOGY
(2022)
Article
Neurosciences
Angela Cheung, Greta Schachermayer, Aude Biehler, Amber Wallis, Megane Missaire, Robert Hindges
Summary: During neurodevelopment, synaptic specificity is driven by interactions between cell adhesion molecules at the synaptic membrane. Teneurins, a family of synaptic adhesion molecules, are involved in regulating neural connectivity establishment. This study found that all four teneurin paralogues are localized to synapses when overexpressed in neurons, with each paralogue distributed differently across pre- and post-synaptic sites. Furthermore, the intracellular domain of teneurin plays an important role in its synaptic localization. The ability of teneurins to form different molecular complexes suggests a higher combinatorial power for generating synaptic specificity than previously thought.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Gabriele Loers, Ralf Kleene, Maria Girbes Minguez, Melitta Schachner
Summary: The interaction between the intracellular domain of cell adhesion molecule L1 and methyl CpG binding protein 2 (MeCP2) affects important functions in neurons, such as neurite outgrowth and migration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Lena Roling, Ansgar Flammersfeld, Gabriele Pradel, Sandra Bennink
Summary: The WD40-repeat protein PfWLP1 plays a crucial role in interacting with adhesion protein complexes in the malaria parasite, essential for the stability and maturation of gametocytes, affecting exflagellation ability.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Sung-Jae Cha, Min-Sik Kim, Chan Hyun Na, Marcelo Jacobs-Lorena
Summary: Plasmodium sporozoites infect the liver after inoculation, where they produce merozoites that infect red blood cells causing malaria symptoms. The HP1 peptide mimics a sporozoite ligand for hepatocyte recognition and partially protects mice from infection by rodent parasites. This mimotope also inhibits human parasite infection of human hepatocytes, showing potential as a novel pre-erythrocytic vaccine candidate.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Hendrik Possemiers, Thao-Thy Pham, Marion Coens, Emilie Pollenus, Sofie Knoops, Sam Noppen, Leen Vandermosten, Sigrid D'haese, Luna Dillemans, Fran Prenen, Dominique Schols, Blandine Franke-Fayard, Philippe E. Van den Steen
Summary: The study showed that parasite sequestration mediated by skeleton binding protein-1 (SBP-1) and high parasite load are not essential for the development of experimental malaria-associated acute respiratory distress syndrome (MA-ARDS), but inhibit the resolution of the disease.
Article
Microbiology
Aline Freville, Margarida Ressurreicao, Christiaan van Ooij
Summary: Malaria parasites alter the host erythrocyte by exporting proteins into it. The presence of a PEXEL motif has been used as a signature for protein export, but this study finds that some proteins remain in the parasitophorous vacuole and are not exported. This challenges the previous understanding of PEXEL and protein processing in malaria parasites.
Article
Multidisciplinary Sciences
Klaas Yperman, Jie Wang, Dominique Eeckhout, Joanna Winkler, Lam Dai Vu, Michael Vandorpe, Peter Grones, Evelien Mylle, Michael Kraus, Romain Merceron, Jonah Nolf, Eliana Mor, Pieter De Bruyn, Remy Loris, Martin Potocky, Savvas N. Savvides, Bert De Rybel, Geert De Jaeger, Daniel Van Damme, Roman Pleskot
Summary: This study reveals the molecular architecture of plant TSET complex and identifies the crucial roles of specific subunits in complex assembly and membrane interaction. The structural differences between the hexameric TSET in Dictyostelium and the octameric TPC in plants are highlighted, advancing the understanding of the endocytosis process.
Article
Biochemistry & Molecular Biology
Kevin J. Hart, B. Joanne Power, Kelly T. Rios, Aswathy Sebastian, Scott E. Lindner
Summary: The NOT1-G paralogue in Plasmodium parasites is crucial for both male and female parasite transmission by regulating mRNA homeostasis, as well as for the development of sexual stages in mosquitoes. Its localization to cytosolic puncta throughout the parasite's life cycle and interaction with other factors play essential roles in ensuring successful transmission. Additionally, the TTP-binding domain of PyNOT1-G is dispensable for its essential blood stage functions but impacts host-to-vector transmission.
Article
Chemistry, Multidisciplinary
Wanhao Cai, Miriam Jaeger, Jakob T. Bullerjahn, Thorsten Hugel, Steffen Wolf, Bizan N. Balzer
Summary: In this study, the rupture force and friction of the biotin-streptavidin complex under a externally applied force were investigated using AFM-based single molecule force spectroscopy and molecular dynamics simulations. Anisotropic friction, arising from an experimentally uncontrolled orientation parameter, was identified. The study suggests that anisotropic friction should be taken into account for a complete understanding of friction in biomolecular dynamics and anisotropic mechanical environments.
Article
Microbiology
Natalie M. Barber, Clinton K. Y. Lau, Louise Turner, Gareth Watson, Susan Thrane, John P. A. Lusingu, Thomas Lavstsen, Matthew K. Higgins
Summary: Structure-guided vaccine design targets key regions of pathogen surfaces to induce focused immune response. A modified protocol focused on PfEMP1 proteins found on red blood cells infected with Plasmodium falciparum. The study successfully grafted EPCR-binding motif of PfEMP1 onto a synthetic scaffold for potential vaccine development.
Editorial Material
Immunology
Matthew K. Higgins
Summary: The study demonstrates that red blood cells infected with Plasmodium falciparum strains commonly found in cerebral malaria patients are specifically internalized by brain endothelial cells, potentially contributing to the symptoms of the disease.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Joao Ramos, Valerie Laux, Michael Haertlein, Elisabetta Boeri Erba, Katherine E. McAuley, V. Trevor Forsyth, Estelle Mossou, Sine Larsen, Annette E. Langkilde
Summary: The study utilized a method to perdeuterate hen egg-white lysozyme, showing that different preparation methods have an impact on the thermal stability and enzymatic activity of the protein, potentially related to protein folding and deuteration effects.
Editorial Material
Parasitology
Alexander D. Cook, Matthew K. Higgins
Summary: Researchers have provided new hope for the development of vaccines against African trypanosomes through a bold, high-throughput screen.
TRENDS IN PARASITOLOGY
(2021)
Article
Biochemical Research Methods
Joao Ramos, Valerie Laux, Michael Haertlein, V. Trevor Forsyth, Estelle Mossou, Sine Larsen, Annette E. Langkilde
Summary: The biological function of a protein is closely related to its structure and dynamics, which are determined by the folding process. In vitro refolding is commonly used to recover recombinant proteins and is important in understanding folding pathways. Different folding modes were observed in hydrogenated and perdeuterated refolded variants, with structural differences impacting thermal stability and enzymatic activity.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Miao Gui, Xiangli Wang, Susan K. Dutcher, Alan Brown, Rui Zhang
Summary: The authors used cryo-EM to build atomic models of the central apparatus of motile cilia from Chlamydomonas reinhardtii and identified 48 different CA-associated proteins. They revealed mechanisms for asymmetric and periodic protein binding to microtubules and discovered a novel class of microtubule inner protein. These structures provide a foundation for further understanding ciliary motility and related diseases.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Hematology
Jacob R. Anderson, Jing Li, Timothy A. Springer, Alan Brown
Summary: This study reveals the structural features and formation mechanism of von Willebrand factor (VWF) tubules using electron cryomicroscopy (cryo-EM), providing a foundation for further understanding of the mutations causing von Willebrand disease (VWD).
Editorial Material
Biochemistry & Molecular Biology
Alan Brown, Franca Fraternali
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Miao Gui, Jacob T. Croft, Davide Zabeo, Vajradhar Acharya, Justin M. Kollman, Thomas Burgoyne, Johanna L. Hoog, Alan Brown
Summary: This study used single-particle cryo-electron microscopy methods to investigate the structure of human ciliary microtubules. Two types of microtubules were studied, and atomic models were built. It was discovered that SPACA9 is a polyspecific microtubule inner protein capable of binding different types of microtubules.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Manuel F. Juette, Jordan D. Carelli, Emily J. Rundlet, Alan Brown, Sichen Shao, Angelica Ferguson, Michael R. Wasserman, Mikael Holm, Jack Taunton, Scott C. Blanchard
Summary: This study determines how the natural products didemnin B and ternatin-4 inhibit translational elongation on mammalian ribosomes using single-molecule fluorescence imaging and cryogenic electron microscopy. These natural products trap the elongation factor eEF1A in an intermediate state of aa-tRNA selection, preventing translation. The study also reveals that didemnin B and ternatin-4 have different effects on the dynamics of aa-tRNA selection, explaining the observed differences in their inhibition efficacies and physiological impacts.
Article
Biochemistry & Molecular Biology
Shimi Meleppattu, Haixia Zhou, Jin Dai, Miao Gui, Alan Brown
Summary: This study determined the structures of native IFT-A complexes using cryo-EM and found that subcomplex rearrangements enable IFT-A to polymerize on anterograde IFT trains. The study also discovered that binding of IFT-A to IFT-B shields the preferred lipid-binding interface and orients a network of b-propeller domains towards the ciliary membrane, capable of accommodating diverse cargoes.
Article
Biochemistry & Molecular Biology
Miguel Ricardo Leung, Jianwei Zeng, Xiangli Wang, Marc C. Roelofs, Wei Huang, Riccardo Zenezini Chiozzi, Johannes F. Hevler, Albert J. R. Heck, Susan K. Dutcher, Alan Brown, Rui Zhang, Tzviya Zeev-Ben-Mordehai
Summary: Sperm motility is crucial for successful reproduction, but the ornamentation of axonemal microtubules and its support for motility in different fertilization environments are unclear. This study investigates native axonemal doublet microtubules (DMTs) in sea urchin and bovine sperm and identifies over 60 proteins decorating DMTs, including those linked to infertility. Through analyzing DMTs across species and cell types, the study defines core microtubule inner proteins (MIPs) and examines the evolution of the tektin bundle. Furthermore, a testis-specific serine/threonine kinase that connects DMTs to outer dense fibers in mammalian sperm is identified. The study provides structural insights into sperm evolution, motility, and dysfunction at a molecular level.
Article
Multidisciplinary Sciences
Travis Walton, Miao Gui, Simona Velkova, Mahmoud R. Fassad, Robert A. Hirst, Eric Haarman, Christopher O'Callaghan, Mathieu Bottier, Thomas Burgoyne, Hannah M. Mitchison, Alan Brown
Summary: The recent research achievements have determined the atomic models of the 96-nm modular repeats of axonemes, revealing the conservation and specialization of axonemes and the mechanisms that regulate ciliary motility. The structures of respiratory-cilia doublet microtubules from individuals with PCD have shown how the loss of individual docking factors can selectively eradicate periodically repeating structures.
Article
Multidisciplinary Sciences
Re'em Moskovitz, Tossapol Pholcharee, Sophia M. DonVito, Bora Guloglu, Edward Lowe, Franziska Mohring, Robert W. Moon, Matthew K. Higgins
Summary: The symptoms of malaria occur during the blood stage of infection, when the parasite replicates within human red blood cells. In this study, the researchers investigated the interaction between the human DARC receptor and the Plasmodium vivax Duffy-binding protein (PvDBP) during the invasion of reticulocytes. They found that a sulphate on tyrosine 41 of DARC binds to a charged pocket on PvDBP, confirming the importance of this interaction. The research also identified the epitope for vaccine-elicited growth-inhibitory antibody DB1, providing valuable information for the design of vaccines and therapeutics to target this essential interaction.
NATURE COMMUNICATIONS
(2023)
Article
Parasitology
Alexander D. Cook, Mark Carrington, Matthew K. Higgins
Summary: This article reviews decades of evidence on the effect of complement on African trypanosomes, focusing on the discovery of a trypanosome receptor for complement C3. It critically assesses three recent studies that attempt to provide a structural and mechanistic view of how this receptor helps trypanosomes survive in the presence of complement.
TRENDS IN PARASITOLOGY
(2023)