Article
Multidisciplinary Sciences
Xingya Xu, Ryuta Kanai, Li Wang, Mitsuhiro Yanagida
Summary: The ATPase activities of cohesin play an important role in chromosome segregation, and mutations in these activities can be compensated through various mechanisms, including changes in coiled coil structure and DNA binding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Mario Cano-Munoz, Samuel Jurado, Bertrand Morel, Francisco Conejero-Lara
Summary: The study highlights the crucial role of the HP in 6HB formation during HIV-1 infection. By investigating the binding behavior of the fluorescent dye ANS to the HP, potential lead compounds for HIV-1 therapeutics targeting the HP were identified. The study also reveals the influence of CHR peptide binding and allosteric connections on the conformational flexibility of the HP, providing insights for the development of small-molecule HIV-1 inhibitors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Multidisciplinary Sciences
Anokhi Shah, Michael J. Taylor, Giulia Molinaro, Sellamuthu Anbu, Margaux Verdu, Lucy Jennings, Iuliia Mikulska, Sofia Diaz-Moreno, Hassane EL Mkami, Graham M. Smith, Melanie M. Britton, Janet E. Lovett, Anna F. A. Peacock
Summary: We report the creation of a new copper-binding site within a protein scaffold, which shows promise as an MRI contrast agent despite the general belief that copper is unsuitable for this purpose. The copper coiled coil displays relaxivity values equal to or better than those of the Gd(III) analog, challenging the current consensus. This study demonstrates the power of de novo peptide design in accessing abiological chemistry for practical applications.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Multidisciplinary
Eesha Khare, Darshdeep S. Grewal, Markus J. Buehler
Summary: Dynamic noncovalent interactions play a crucial role in the structure and function of biological proteins and have been explored in bioinspired materials. Metal-coordination bonds offer tunability and can control the properties of synthetic materials. However, understanding the exact contribution of these bonds towards mechanical strength and the effect of geometric arrangements is lacking. In this study, we engineer the cooperative rupture of metal-coordination bonds to enhance the rupture strength of metal-coordinated peptide dimers, and we provide quantitative insights into the cooperativity and intrinsic strength limit of these bonds. This work aims to advance the molecular design principles for metal-coordinated materials.
Article
Cell Biology
Shoichiro Ono, Eichi Watabe, Keita Morisaki, Kanako Ono, Hidehito Kuroyanagi
Summary: This study discovered a novel alternative exon in the Caenorhabditis elegans tropomyosin gene and investigated the effects of alternative splicing on tropomyosin isoforms. In vitro experiments showed that the isoform containing the alternative exon had poor binding affinity to actin filaments. Mutations in the alternative exon resulted in reduced motility and brood size, suggesting its importance for optimal health.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Microbiology
Juan A. Torres, Rebecca R. Pasquarelli, Peter S. Back, Andy S. Moon, Peter J. Bradley
Summary: The study identifies a novel component of the Toxoplasma gondii IMC, IMC32, which is essential for parasite survival by localizing to developing daughter buds early during endodyogeny. IMC32's localization depends on specific structural domains, and two conserved regions within the C-terminal coiled-coil domains are critical for its function during replication. This provides a potential new therapeutic target for T. gondii and related apicomplexan parasites.
Article
Biochemistry & Molecular Biology
Hana Popelka, Erin F. Reinhart, Shree Padma Metur, Kelsie A. Leary, Michael J. Ragusa, Daniel J. Klionsky
Summary: The role of Atg16 in macroautophagy involves two distinct characteristics - acting as a homodimer and as a peripheral membrane-binding polypeptide. These traits are determined by two different regions of Atg16, with one responsible for membrane binding and the other essential for homodimer formation.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
W. Clifford Boldridge, Ajasja Ljubetic, Hwangbeom Kim, Nathan Lubock, Daniel Szilagyi, Jonathan Lee, Andrej Brodnik, Roman Jerala, Sriram Kosuri
Summary: The authors developed an assay and computational methods to identify more orthogonal coiled-coil pairs, which are crucial for biological processes and drug design.
NATURE COMMUNICATIONS
(2023)
Article
Plant Sciences
Zhizheng Wang, Jin Huang, Lingyun Nie, Yinxia Hu, Ning Zhang, Qin Guo, Jianping Guo, Bo Du, Lili Zhu, Guangcun He, Rongzhi Chen
Summary: The study reveals that the BPH9 gene encodes a protein that regulates plant resistance to brown planthopper through associations between its CC, NBS, and LRR domains, with NBS2 acting as a molecular switch. Further experiments showed that the CC domains of BPH9 and susceptible alleles have similar abilities to induce resistance and hypersensitive response, while the LRR domain of BPH9 provides resistance specificity.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Chemistry, Multidisciplinary
Hermann Neitz, Niels Benjamin Paul, Florian R. Hage, Christina Lindner, Roman Graebner, Michael Kovermann, Franziska Thomas
Summary: The study presents a combinatorial approach to identify novel functional mini-proteins based on the WW-domain scaffold. The WW domain fragments were reconstituted through coiled coil association, and the binding properties were fully restored. Using this approach, specific binding domains for ATP and phosphorylcholine were identified.
Article
Biochemistry & Molecular Biology
Parastou Rahimizadeh, Jeong Eun Lee, Dae-Hee Lee, Sung In Lim
Summary: Human serum albumin (HSA) is a biocompatible half-life extender that can increase the survival time of protein-based therapeutics. Researchers have developed a novel HSA variant (eHSA) that is compatible with any protein payload and can retain the activity of the payload. This study demonstrates that eHSA could serve as a modular platform for delivering various therapeutic proteins with potentially long half-lives.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Eliza C. Martin, Catalin F. Ion, Florin Ifrimescu, Laurentiu Spiridon, Jaap Bakker, Aska Goverse, Andrei-J Petrescu
Summary: NLRscape is a webserver that hosts a collection of over 80,000 plant protein sequences and provides various tools for exploring the complex sequence landscape of this class of proteins. Users can analyze the distribution of NLR family sequence features in the plant kingdom using different analytical tools.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biology
Ruben Hervas, Maria del Carmen Fernandez-Ramirez, Albert Galera-Prat, Mari Suzuki, Yoshitaka Nagai, Marta Bruix, Margarita Menendez, Douglas V. Laurents, Mariano Carrion-Vazquez
Summary: The divergent prion-like domains (PLDs) of CPEB proteins from different species retain the ability to form a generic amyloid-like fold through different assembly mechanisms, with structural differences at the beginning of their amyloid assembly pathways.
Review
Cell Biology
Huan Wang, Ling Zhang, Qiuhua Luo, Jia Liu, Guiling Wang
Summary: The microrchidia (MORC) family of proteins is highly conserved and plays diverse biological functions, with a focus on their role as epigenetic regulators and in chromatin remodeling. While originally identified in germ cell development, MORCs are now recognized as disease genes and oncogenes, making them potentially important biomarkers for diagnosis and treatment in human disorders and cancer. The expanding understanding of the MORC family's function has highlighted their potential as targets for developing tools and treatments for human diseases, including cancers.
CELL DEATH & DISEASE
(2021)
Review
Cell Biology
Italo A. Cavini, Diego A. Leonardo, Higor V. D. Rosa, Danielle K. S. V. Castro, Humberto D'Muniz Pereira, Napoleao F. Valadares, Ana P. U. Araujo, Richard C. Garratt
Summary: Understanding the three-dimensional structures of molecular components in biochemical systems, such as septins, is crucial for unraveling their mechanistic functions. Recent advances have provided more detailed insights into the structural basis of higher-order septin assemblies, although further research is needed to fully understand their physiological roles and interactions with cellular components.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Ronja Gohde, Benjamin Naumann, Davis Laundon, Cordelia Imig, Kent McDonald, Benjamin H. Cooper, Frederique Varoqueaux, Dirk Fasshauer, Pawel Burkhardt
Summary: Neurosecretory vesicles play a crucial role in cell-cell signaling in animals, with a conserved protein composition among bilaterians suggesting a common evolutionary origin. While little is known about these vesicles in non-bilaterian organisms, most core neurosecretory vesicle proteins have been identified in unicellular organisms. The presence of key neurosecretory vesicle proteins in unicellular organisms provides insights into the ancestral molecular machinery of these vesicles.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2021)
Article
Cell Biology
Daria Y. Romanova, Frederique Varoqueaux, Jean Daraspe, Mikhail A. Nikitin, Michael Eitel, Dirk Fasshauer, Leonid L. Moroz
Summary: Placozoans are among the simplest free-living animals, with bodies consisting of three cell layers and roughly seven major cell types. They lack muscle cells and neurons but are able to move using ciliated surfaces and coordinate food intake. Recent research has revealed a higher level of cell-type diversity in placozoans than previously anticipated.
CELL AND TISSUE RESEARCH
(2021)
Article
Neurosciences
Mathias A. Boehme, Anthony W. McCarthy, Natalie Blaum, Monika Berezeckaja, Kristina Ponimaskine, David Schwefel, Alexander M. Walter
Summary: Our study identifies the crucial role of non-neuronal Synaptobrevin (Syb) in Drosophila peripheral glia, showing its importance in maintaining proper glial-glial and glial-neural interactions for adequate nerve function, animal motility, and survival. Syb is necessary for various glial subtypes, impacting nerve morphology, axonal transport, and locomotion. The findings highlight the essential role of Syb in different glial subtypes and its impact on overall nerve function and animal behavior.
Article
Multidisciplinary Sciences
Kaitlyn McGrath, Shivani Agarwal, Marco Tonelli, Mykola Dergai, Anthony L. Gaeta, Andrew K. Shum, Jessica Lacoste, Yongbo Zhang, Wenyu Wen, Daayun Chung, Grant Wiersum, Aishwarya Shevade, Sofia Zaichick, Damian B. van Rossum, Ludmilla Shuvalova, Jeffrey N. Savas, Sergei Kuchin, Mikko Taipale, Kim A. Caldwell, Guy A. Caldwell, Dirk Fasshauer, Gabriela Caraveo
Summary: Ykt6, a soluble SNARE protein, plays a critical role in vesicular fusion pathways. Phosphorylation at a conserved site triggers a conformational change, leading to altered protein interactions and enhanced toxicity in PD models. This study reveals a mechanism regulating Ykt6 conformation and activity with potential implications for Parkinson's disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Bassam Tawfik, Joana S. Martins, Sebastien Houy, Cordelia Imig, Paulo S. Pinheiro, Sonja M. Wojcik, Nils Brose, Benjamin H. Cooper, Jakob Balslev Sorensen
Summary: Synaptotagmin-1 and synaptotagmin-7 act as fast and slow calcium sensors independently in vesicle fusion, with non-overlapping distributions when coexpressed. Synaptotagmin-7 promotes vesicle priming and inhibits depriming, affecting the fusion mediated by synaptotagmin-1. Both synergistic and competitive interactions are observed between synaptotagmin-1 and synaptotagmin-7.
Editorial Material
Neurosciences
Magnus Kjaergaard, Nicolas Caesar Petersen, Jakob Balslev Sorensen, Tomonori Takeuchi
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Cell Biology
Dany Khalifeh, Emilie Neveu, Dirk Fasshauer
Summary: Many intracellular pathogens, including bacteria and large viruses, modify vesicle trafficking within host cells to avoid degradation. Recent studies have found SNARE proteins, which are core machinery for vesicle fusion, encoded in the genomes of pathogenic bacteria and giant viruses. These findings suggest that both bacteria and viruses interfere with host vesicle trafficking and utilize a repertoire of trafficking factors.
Article
Biology
Janus R. L. Kobbersmed, Manon M. M. Berns, Susanne Ditlevsen, Jakob B. Sorensen, Alexander M. Walter
Summary: Synaptic communication relies on the fusion of synaptic vesicles with the plasma membrane, which is achieved through the allosteric stabilization of synaptotagmin's Ca2+/PI(4,5)P-2 dual-bound state and the coordinated function of multiple synaptotagmins.
Article
Biology
Sebastien Houy, Joana S. Martins, Noa Lipstein, Jakob Balslev Sorensen
Summary: This study investigated the relationship between phorbolesters and Munc13-1 and ubMunc13-2, and found that phorbolesters only stimulated secretion when ubMunc13-2 was dominant. The results showed that DAG/phorbolesters, ubMunc13-2, and Syt7 are important factors for stimulating dense-core vesicle priming.
Article
Biochemistry & Molecular Biology
Julika Radecke, Raphaela Seeger, Anna Kadkova, Ulrike Laugks, Amin Khosrozadeh, Kenneth N. Goldie, Vladan Lucic, Jakob B. Sorensen, Benoit Zuber
Summary: This study used cryo-electron tomography to observe the intermediate steps following synaptic stimulation, and found that during the early fusion stage after stimulation, synaptic vesicles undergo morphological changes to establish contact with the plasma membrane. The subsequent late fusion stage results in fusion pore opening and collapse of the synaptic vesicles. These morphological observations likely correspond to the transition of synaptic vesicles from one functional pool to another.
Article
Neurosciences
Andreas T. Grasskamp, Meida Jusyte, Anthony W. McCarthy, Torsten W. B. Goetz, Susanne Ditlevsen, Alexander M. Walter
Summary: Synaptic transmission relies on the release of neurotransmitter from synaptic vesicles and its detection by postsynaptic receptors. There are two principal modes of transmission: action-potential evoked and spontaneous transmission. This study investigates the functional interdependence of these modes at individual synaptic contacts in Drosophila larval neuromuscular junctions. The results show that spontaneous activity can predict the responsiveness of synapses to action-potential stimulation.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Cell Biology
Meida Jusyte, Natalie Blaum, Mathias A. Boehme, Manon M. M. Berns, Alix E. Bonard, Abel B. Vamosi, Kavya V. Pushpalatha, Janus R. L. Kobbersmed, Alexander M. Walter
Summary: Presynaptic plasticity adjusts neurotransmitter (NT) liberation, with short-term facilitation (STF) and presynaptic homeostatic potentiation (PHP) playing roles in millisecond repetitive activation and stabilizing transmission over minutes, respectively. Functional overlap and shared molecular dependence on Unc13A's release-site protein are observed despite different timescales of STF and PHP. Mutating Unc13A's calmodulin binding domain (CaM-domain) blocks STF and PHP while increasing baseline transmission, suggesting a role for the Ca2+/calmodulin/Unc13A interaction in plastic stabilization of vesicle priming. Acute phorbol ester treatment enhances NT release and blocks STF/PHP in synapses expressing wild-type Unc13A but not in synapses with CaM-domain mutation, indicating common downstream effects. The regulatory domains of Unc13A integrate signals across timescales to regulate release-site participation for synaptic plasticity.
Article
Multidisciplinary Sciences
Tina Ghelani, Marc Escher, Ulrich Thomas, Klara Esch, Janine Luetzkendorf, Harald Depner, Marta Maglione, Pierre Parutto, Scott Gratz, Tanja Matkovic-Rachid, Stefanie Ryglewski, Alexander M. Walter, David Holcman, Kate O'Connor Giles, Martin Heine, Stephan J. Sigrist
Summary: In this study, dynamic intravital single-molecule imaging was used to investigate the interaction between scaffold proteins and voltage-gated calcium channels (VGCCs) during presynaptic homeostatic potentiation in Drosophila AZs. It was found that the interaction between the intracellular carboxyl terminus of the Cac channel and the amino-terminal region of the ELKS-family protein Bruchpilot played a crucial role in the sustained potentiation of AZs.
Article
Biology
Ariane Ernst, Nathalie Unger, Christof Schuette, Alexander M. Walter, Stefanie Winkelmann
Summary: At active zones of chemical synapses, fusion of vesicles and presynaptic membrane occur upon arrival of electric signal, releasing neurotransmitters into synaptic cleft. The recovery process of both release sites and vesicles after fusion is of interest to understand the rate-limiting step in high-frequency sustained stimulation. A non-linear reaction network is used to investigate this problem, showing that neither vesicle nor release site recovery step is essential, and the rate-limiting feature changes over time. The dynamics given by ordinary differential equations exhibit transient changes leading to an asymptotic periodic orbit, while the stochastic jump model lacks oscillatory behavior and asymptotic periodicity.
MATHEMATICAL BIOSCIENCES
(2023)