Article
Cell Biology
Paul Lopez, Oluwaseun Ajibola, Amelie Pagliuzza, Romaniya Zayats, Wan Hon Koh, Alon Herschhorn, Nicolas Chomont, Thomas T. Murooka
Summary: The migration of T cells in 3D collagen matrix enhances HIV infection and integration. Migratory T cells are less sensitive to antiretroviral drugs and can freely migrate into regions with high HIV densities, resulting in high infection rates. These findings indicate that the environmental context of initial HIV-T cell encounters modulates HIV-1 entry and integration efficiencies.
Article
Multidisciplinary Sciences
Zeynab Mousavikhamene, Daniel J. Sykora, Milan Mrksich, Neda Bagheri
Summary: This research successfully introduced an algorithm that could distinguish cancer from non-cancer cells in high-resolution single cell images by exploiting structural differences in the cytoskeleton. Overcoming the barrier of insufficient data in machine learning methodologies, the study identified the most discriminatory features to predict cell type accurately with as few as 100 cells per line. Furthermore, normalizing cell shape improved discrimination of cell lines with difficult-to-distinguish phenotypes, demonstrating the generalizability of the algorithm across various tissue origins.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Ka Man Carmen Chan, Ashley L. Arthur, Johannes Morstein, Meiyan Jin, Abrar Bhat, Dorte Schlesinger, Sungmin Son, Donte A. Stevens, David G. Drubin, Daniel A. Fletcher
Summary: Fusion-associated small transmembrane (FAST) proteins are a diverse family of nonstructural viral proteins that drive cell-cell fusion, increasing viral spread and pathogenicity. Unlike viral fusogens with tall ectodomains, FAST proteins have short fusogenic ectodomains that cannot bridge the intermembrane gap between neighboring cells. This work suggests that localized mechanical pressure on the plasma membrane coupled to a membrane-disruptive ectodomain is sufficient to drive cell-cell fusion.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Zeynab Alborzi, Maria-Dolors Piulachs
Summary: The transcription factor Ftz-f1 plays multiple roles in insect development, including the regulation of steroidogenic enzymes in insect ovaries. Injecting dsftz-f1 into female Blattella germanica at different time points prevented oviposition and resulted in changes in gene expression related to steroidogenesis. These findings suggest that Ftz-f1 regulates the expression of steroidogenic genes in B. germanica, with phm possibly being a key target.
INSECT MOLECULAR BIOLOGY
(2023)
Article
Virology
Xin-Man Li, Shi-Ping Wang, Jin-Yuan Wang, Ting Tang, Bo Wan, Lei Zeng, Jiang Wang, Bei-Bei Chu, Guo-Yu Yang, Jia-Jia Pan
Summary: This study reveals that RhoA acts as a host restriction factor in inhibiting PRV replication, and disruption of the actin cytoskeleton reduces virus replication.
Review
Biochemistry & Molecular Biology
Lenka Hornikova, Katerina Brustikova, Sandra Huerfano, Jitka Forstova
Summary: The nuclear lamina is crucial for maintaining the integrity of the cell nucleus, but it poses a barrier for virus replication. Viruses have evolved mechanisms to overcome this obstacle by inducing the assembly of multiprotein complexes and exploiting cellular kinases. Additionally, viruses use nuclear actin for intranuclear particle movement.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Seung-Yeon Joe, Seul-Gi Yang, Jae-Ho Lee, Hyo-Jin Park, Deog-Bon Koo
Summary: This study investigated the effects of paclitaxel, a microtubule stabilizer, on the developmental potential of pig blastocysts. The findings suggest that the stabilization of F-actin cytoskeleton through P38 MAPK activation can improve the developmental competence of pig blastocysts. However, high concentrations of paclitaxel disrupt blastocyst development by causing F-actin aggregation, cytokinesis defects, and over-expression of p-P38 MAPK protein.
Article
Neurosciences
Rita Pinto-Costa, Monica Mendes Sousa
Summary: Cytolinkers play a crucial role in ensuring the integration of different cytoskeleton components in neurons, which is essential for proper function and connectivity of high order circuits. Several cytoskeleton regulatory proteins with actin-microtubule crosslinking activity have been identified as important players in axon outgrowth and guidance.
NEUROSCIENCE LETTERS
(2021)
Article
Pharmacology & Pharmacy
Minqi Liang, Yizhe Li, Kexin Zhang, Yujia Zhu, Jingyao Liang, Minjie Liu, Shuqing Zhang, Delin Chen, Hao Liang, Linyue Liang, Shu An, Xun Zhu, Zhenjian He
Summary: In this study, we found that the host factor DUSP5 was upregulated after dengue virus infection and demonstrated its role in inhibiting viral replication. DUSP5 restricts viral entry into host cells by negatively regulating the ERK-MLCK-Myosin IIB signaling axis and suppressing F-actin rearrangement. Furthermore, DUSP5 exhibits broad-spectrum antiviral effects against dengue and Zika viruses.
ANTIVIRAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Yan-Fang Zhang, Shu-Tong Chen, Yun Gao, Long Yang, Hua Yu
Summary: Nicotiana alata, widely used in landscaping, has both ornamental and commercial/medical value. The global potential habitat and environmental factors affecting its distribution are not well understood. In this study, the MaxEnt model was used to predict the global suitable habitats of N. alata under current and future climate conditions. The results identified key bioclimatic variables and revealed the distribution patterns of N. alata. The findings provide valuable information for the reasonable planting of N. alata.
SCIENTIFIC REPORTS
(2023)
Article
Neurosciences
Tanushree Kundu, Sooraj Siva Das, Lisas K. Sewatkar, Divya S. Kumar, Dhriti Nagar, Aurnab Ghose
Summary: The study found that Fmn2 regulates the formation of axonal collateral protrusions in chick and zebrafish, localizing to the protrusion-initiating axonal F-actin patches and regulating their lifetime and size. The F-actin nucleation activity of Fmn2 is necessary for patch stability but not for patch formation. Fmn2 insulates the F-actin patches from disassembly by ADF, promoting long-lived, larger patches that can initiate axonal protrusions.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Liyuan Xu, Lingyan Cao, Jiejie Li, Christopher J. Staiger
Summary: By combining genetic and small molecule inhibitor approaches, this study reveals the roles of two classes of actin filament nucleator in maintaining the homeostatic cortical cytoskeleton array in Arabidopsis epidermal cells. The findings suggest that multiple actin nucleation mechanisms cooperate to generate and maintain the unique cytoskeletal arrays within a common cytoplasm.
Article
Multidisciplinary Sciences
Biljana Ermanoska, Bob Asselbergh, Laura Morant, Maria-Luise Petrovic-Erfurth, Seyyedmohsen Hosseinibarkooie, Ricardo Leitao-Goncalves, Leonardo Almeida-Souza, Sven Bervoets, Litao Sun, LaTasha Lee, Derek Atkinson, Akram Khanghahi, Ivaylo Tournev, Patrick Callaerts, Patrik Verstreken, Xiang-Lei Yang, Brunhilde Wirth, Avital A. Rodal, Vincent Timmerman, Bruce L. Goode, Tanja A. Godenschwege, Albena Jordanova
Summary: Mutations in tyrosyl-tRNA synthetase and other tRNA ligases cause Charcot-Marie-Tooth peripheral neuropathy, with dysregulation of F-actin organization playing a role. A gain-of-function mechanism is implicated in the pathogenicity. Genetic modulation of F-actin improves neuronal features in flies expressing the disease-causing mutations. This study reveals the evolutionary-conserved role of YARS1 as an F-actin organizer and its link to tRNA-synthetase-induced neurodegeneration.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Ryan K. Hylton, Jessica E. Heebner, Michael A. Grillo, Matthew T. Swulius
Summary: In this study, the authors demonstrate that filopodial actin filaments switch between bundles of fascin-crosslinked actin and cofilin-decorated filaments. The authors also observe that cofilactin is associated with various dynamic events within filopodia. Furthermore, the hyper-twisting of actin due to cofilin binding leads to a rearrangement of filament packing, which excludes fascin from the base of filopodia.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Remi Mascarau, Marie Woottum, Lea Fromont, Remi Gence, Vincent Cantaloube-Ferrieu, Zoi Vahlas, Kevin Leveque, Florent Bertrand, Thomas Beunon, Arnaud Metais, Hicham El Costa, Nabila Jabrane-Ferrat, Yohan Gallois, Nicolas Guibert, Jean-Luc Davignon, Gilles Favre, Isabelle Maridonneau-Parini, Renaud Poincloux, Bernard Lagane, Serge Benichou, Brigitte Raynaud-Messina, Christel Verollet
Summary: Mascarau et al. demonstrate the relevance of HIV-1 infection of tissue-resident macrophages by fusion with infected CD4(+) T cells and show that this process is modulated by the macrophage activation state and is under the control of the CD81/RhoA/Myosin axis. Macrophages play a critical role in HIV-1 pathogenesis and serve as major viral reservoirs. Understanding macrophage infection, especially in tissue macrophages, is crucial for understanding the persistence of the virus in patients.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Elizabeth Ramos-Morales, Efil Bayam, Jordi Del-Pozo-Rodriguez, Thalia Salinas-Giege, Martin Marek, Peggy Tilly, Philippe Wolff, Edouard Troesch, Eric Ennifar, Laurence Drouard, Juliette D. Godin, Christophe Romier
Summary: This study provides insights into the molecular mechanisms of tRNA deamination by ADAT2 and the importance of the ADAT3 N-terminal domain in tRNA binding and deamination. The rotation of the N-terminal domain with respect to the catalytic domain plays a crucial role in presenting and positioning the tRNA anticodon-stem-loop correctly in the ADAT2 active site. A founder mutation in the ADAT3 N-terminal domain, causing intellectual disability, is shown to hinder optimal presentation of the tRNA anticodon-stem-loop to ADAT2.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Andrea Schenkmayerova, Gaspar P. Pinto, Martin Toul, Martin Marek, Lenka Hernychova, Joan Planas-Iglesias, Veronika Daniel Liskova, Daniel Pluskal, Michal Vasina, Stephane Emond, Mark Doerr, Radka Chaloupkova, David Bednar, Zbynek Prokop, Florian Hollfelder, Uwe T. Bornscheuer, Jiri Damborsky
Summary: This study presents a protein-engineering framework based on InDel mutagenesis and fragment transplantation, leading to improved catalysis and longer glow-type bioluminescence of the ancestral luciferase. The research tracks the role of dynamics in evolution, revealing the importance of protein dynamics in functional innovation.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Klara Markova, Antonin Kunka, Klaudia Chmelova, Martin Havlasek, Petra Babkova, Sergio M. Marques, Michal Vasina, Joan Planas-Iglesias, Radka Chaloupkova, David Bednar, Zbynek Prokop, Jiri Damborsky, Martin Marek
Summary: Enzyme functionality depends on its unique three-dimensional structure, with computational algorithms being used to stabilize proteins for research and biotech applications. In a unique case, introducing eleven stabilizing mutations affected the protein folding energy landscape and resulted in advantageous catalytic domain-swapped dimers.
Article
Cell Biology
Martin Marek, Elizabeth Ramos-Morales, Gisele F. A. Picchi-Constante, Theresa Bayer, Carina Norstrom, Daniel Herp, Policarpo A. Sales-Junior, Eloise P. Guerra-Slompo, Kristin Hausmann, Alokta Chakrabarti, Tajith B. Shaik, Annika Merz, Edouard Troesch, Karin Schmidtkunz, Samuel Goldenberg, Raymond J. Pierce, Marina M. Mourao, Manfred Jung, Johan Schultz, Wolfgang Sippl, Nilson I. T. Zanchin, Christophe Romier
Summary: The zinc-dependent histone deacetylases in the protozoan parasite Trypanosoma cruzi have significantly diverged from their human counterparts, with tcDAC2 displaying essential deacetylase activity and major structural differences. Targeting these atypical HDACs can lead to selective chemical impairment of parasites.
Article
Chemistry, Physical
Martin Toul, Dmitri Nikitin, Martin Marek, Jiri Damborsky, Zbynek Prokop
Summary: This study provides a detailed understanding of the biochemical mechanism and limiting steps of the plasminogen activator staphylokinase, and determines its high catalytic activity. This knowledge is crucial for fully understanding its catalytic functionality and designing rational engineering strategies.
Article
Clinical Neurology
Martin Toul, Jan Mican, Veronika Slonkova, Dmitri Nikitin, Martin Marek, David Bednar, Jiri Damborsky, Zbynek Prokop
Summary: The burden of strokes is increasing, and current therapeutic drugs are not ideal. Staphylokinase has been identified as a potential thrombolytic agent that is efficient, fibrin-selective, inexpensive, and can evolve. Recent findings have shown that a nonimmunogenic variant of staphylokinase is comparable to alteplase, with a reduced risk of intracranial hemorrhage and the advantage of single bolus administration. Furthermore, detailed analysis has revealed a bottleneck in staphylokinase's activity that, if eliminated, could provide up to 1000-fold higher activity than alteplase. These limitations provide new possibilities for improvement by protein engineers.
Article
Chemistry, Physical
Andrea Schenkmayerova, Martin Toul, Daniel Pluskal, Racha Baatallah, Glwadys Gagnot, Gaspar P. P. Pinto, Vinicius T. T. Santana, Marketa Stuchla, Petr Neugebauer, Pimchai Chaiyen, Jiri Damborsky, David Bednar, Yves L. L. Janin, Zbynek Prokop, Martin Marek
Summary: Through crystallographic, spectroscopic, and computational experiments, we have unraveled the oxidative mechanism by which the coelenterazine-powered Renilla luciferase generates blue photons. The study reveals the key role of deprotonated imidazopyrazinone and aspartate residues in the catalytic process. These findings provide insights for the development of more sensitive optical bioassays.
Article
Neurosciences
Michal Nemergut, Sergio M. Marques, Lukas Uhrik, Tereza Vanova, Marketa Nezvedova, Darshak Chandulal Gadara, Durga Jha, Jan Tulis, Veronika Novakova, Joan Planas-Iglesias, Antonin Kunka, Anthony Legrand, Hana Hribkova, Veronika Pospisilova, Jiri Sedmik, Jan Raska, Zbynek Prokop, Jiri Damborsky, Dasa Bohaciakova, Zdenek Spacil, Lenka Hernychova, David Bednar, Martin Marek
Summary: This study reveals the molecular mechanism of ApoE4 aggregation and identifies a potential drug candidate for treatment. The results connect the structure of ApoE4 with its propensity for aggregation, offering a new druggable target for neurodegenerative diseases and aging.
MOLECULAR NEURODEGENERATION
(2023)
Article
Biochemical Research Methods
Eloise Pavao Guerra-Slompo, Gisele Fernanda Assine Picchi-Constante, Martin Marek, Christophe Romier, Wolfgang Sippl, Nilson Ivo Tonin Zanchin
Summary: We present a combined in cellulo and in vivo approach to identify compounds with high potential for inhibiting Trypanosoma cruzi. The in cellulo assays consist of two phases - one for excluding inactive or toxic compounds and the other for determining IC50, CC50, and selective index (SI). Compounds with high SI are further tested in in vivo infection models to evaluate their efficacy compared to benznidazole, a reference drug for Chagas disease treatment. For more details, refer to Marek et al. (2021).
Article
Environmental Sciences
Michal Nemergut, Tereza Batkova, Dana Vigasova, Milan Bartos, Martina Hlozankova, Andrea Schenkmayerova, Barbora Liskova, Katerina Sheardova, Martin Vyhnalek, Jakub Hort, Jan Laczo, Ingrid Kovacova, Michal Sitina, Radoslav Matej, Radim Jancalek, Martin Marek, Jiri Damborsky
Summary: This study found a higher frequency rate of AD patients testing positive for Treponema spp. and a higher occurrence of cases with multiple simultaneous infections in AD patients. These findings provide further evidence of the association between microbial infections and AD and suggest that parallel analysis of multiple sample specimens is advisable for future studies.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Chemistry, Multidisciplinary
Sergio M. Marques, Michaela Slanska, Klaudia Chmelova, Radka Chaloupkova, Martin Marek, Spencer Clark, Jiri Damborsky, Eric T. Kool, David Bodnar, Zbynek Prokop
Summary: HaloTag labeling technology has revolutionized protein chemistry and cellular biology, and a systematic analysis of different ligands has led to the discovery of an optimal protein tag selection protocol, eliminating the need for expensive and complex protein engineering.
Article
Biochemical Research Methods
Gisele Fernanda Assine Picchi-Constante, Priscila Mazzocchi Hiraiwa, Martin Marek, Vanessa Zulkievicz Rogerio, Eloise Pavao Guerra-Slompo, Christophe Romier, Nilson Ivo Tonin Zanchin
Summary: This study presents a novel genetic complementation strategy for investigating gene function in Trypanosoma cruzi, the parasite responsible for Chagas disease. By combining CRISPR-Cas9 technology with recombination of resistant variants of the target gene containing desired mutations, detailed exploration of protein function is made possible. This experimental approach overcomes some of the limitations associated with traditional gene knockouts in T. cruzi.
Article
Biochemistry & Molecular Biology
Petra Babkova, Zuzana Dunajova, Radka Chaloupkova, Jiri Damborsky, David Bednar, Martin Marek
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Martin Marek, Radka Chaloupkova, Tatyana Prudnikova, Yukari Sato, Pavlina Rezacova, Yuji Nagata, Ivana Kuta Smatanova, Jiri Damborsky
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2020)
Article
Chemistry, Multidisciplinary
Klara Markova, Klaudia Chmelova, Sergio M. Marques, Philippe Carpentier, David Bednar, Jiri Damborsky, Martin Marek
