Article
Biochemistry & Molecular Biology
Dong Chen, Siyuan Xia, Rukang Zhang, Yuancheng Li, Christopher A. Famulare, Hao Fan, Rong Wu, Mei Wang, Allen C. Zhu, Shannon E. Elf, Rui Su, Lei Dong, Martha Arellano, William G. Blum, Hui Mao, Sagar Lonial, Wendy Stock, Olatoyosi Odenike, Michelle Le Beau, Titus J. Boggon, Chuan He, Jianjun Chen, Xue Gao, Ross L. Levine, Jing Chen
Summary: The study revealed that mutant IDH2 in AML cells commonly has K413 acetylation, which negatively regulates its activity by attenuating dimerization and blocking substrate and cofactor binding. K413 acetylation of mitochondrial mIDH2 is achieved through a series of hierarchical phosphorylation events, optimizing the leukemogenic ability of mIDH2 in AML cells.
Article
Microbiology
Xinghong Zhao, Xiaoqi Wang, Rhythm Shukla, Raj Kumar, Markus Weingarth, Eefjan Breukink, Oscar P. Kuipers
Summary: Lipo-tridecapeptides are effective against Gram-positive pathogens, but often exhibit high hemolytic activity and cytotoxicity, limiting their potential as antibiotics. However, a novel lipo-tridecapeptide, brevibacillin 2V, shows low hemolytic activity and cytotoxicity, and acts as a bactericidal agent against MRSA by binding to and permeabilizing the bacterial membrane. This study provides insight into the antimicrobial mode of action of brevibacillin 2V, aiding in its development as an alternative antimicrobial agent.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Lena Quambusch, Laura Depta, Ina Landel, Melissa Lubeck, Tonia Kirschner, Jonas Nabert, Niklas Uhlenbrock, Joern Weisner, Michael Kostka, Laura M. Levy, Carsten Schultz-Fademrecht, Franziska Glanemann, Kristina Althoff, Matthias P. Mueller, Jens T. Siveke, Daniel Rauh
Summary: The study focuses on elucidating the specific effects of protein kinase Akt isoforms by establishing an Akt isoform-dependent cellular model system and developing isoform-selective covalent-allosteric Akt inhibitors through X-ray crystallography and structure-based ligand design. This approach allows for the study of isoform-selective effects of Akt inhibition in cancer cells, potentially paving the way for the development of next-generation therapeutics with superior on-target properties.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Li Xuan Sun, Yvonne Shuen Lann Choo, Wei Ting Gao, Xue Lang Gao, Jia Hui Chen, Zhi Hong Cai, Jia Jun Wang, Qiu Gen Zhang, Ai Mei Zhu, Qing Lin Liu
Summary: In recent years, the microphase separation structure of ion-exchange membranes constructed by intermolecular interaction forces has received extensive attention, with porphyrins providing an active self-aggregation driving force through pi-pi interaction. By introducing porphyrins, a series of highly efficient ion channels have been designed and fabricated, demonstrating good OH- conductivity and relatively low IEC. This porphyrin self-assembled strategy offers an effective way to develop AEMs with desirable properties.
ACS APPLIED ENERGY MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Farnaz Hemmati, Ayuba Akinpelu, Jiyeon Song, Farshad Amiri, Anya McDaniel, Collins McMurray, Alexandros Afthinos, Stelios T. T. Andreadis, Andrew V. V. Aitken, Vinicia C. C. Biancardi, Sharon Gerecht, Panagiotis Mistriotis
Summary: Cell migration through confining 3D topographies can lead to detrimental effects such as loss of nuclear envelope integrity and DNA damage. However, cells exposed to long-term confinement do not usually die. This study utilizes photopatterning and microfluidics to develop a high-throughput device for prolonged culture of single cells in microchannels. The results show that continuous exposure to tight confinement can trigger nuclear envelope rupture events and promote cell apoptosis.
Article
Immunology
Xiao-Na Liu, Li-Wei Li, Fei Gao, Yi-Feng Jiang, Wan-Zhe Yuan, Guo-Xin Li, Ling-Xue Yu, Yan-Jun Zhou, Guang-Zhi Tong, Kuan Zhao
Summary: The study found that cGAS increases the production of IFN-beta during PRRSV infection, restricts the replication of PRRSV, and damaged mitochondria leading to mtDNA leakage further activates cGAS, enhancing its activity to combat the virus.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Geraldine Veeckmans, Emily Van San, Tom Vanden Berghe
Summary: Ferroptosis is a cell death mechanism that occurs through excessive peroxidation of polyunsaturated fatty acids within cellular membranes, catalyzed by iron. This process is tightly regulated by lipid, iron, and redox metabolic processes. This review provides an overview of how ferroptosis is executed, including the major classes of inducers and inhibitors, as well as methods for detection. The detrimental role of ferroptosis in disease is also briefly discussed.
Review
Biochemistry & Molecular Biology
Fatemeh Rezaei, Danny Farhat, Gonca Gursu, Sabrina Samnani, Jyh-Yeuan Lee
Summary: The subfamily-G ATP-binding cassette (ABCG) transporters are important for regulating cholesterol homeostasis. Recent structural data of ABCG1 and ABCG5/G8 reveal potential sterol binding sites and a proposed cholesterol translocation pathway. Both ABCG1 and ABCG5/G8 share similar overall molecular architecture and use unique structural motifs, such as the phenylalanine highway and hydrophobic valve, to facilitate cholesterol transport. However, ABCG1 exclusively transports cholesterol while ABCG5/G8 can transport both cholesterol and phytosterols. Ligand docking analysis suggests differences in recruiting sterol molecules to their binding sites. This article discusses the relevance of different and shared structural features to their physiological functions and provides perspectives for future studies on ABCG cholesterol transporters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Xiao Yang, Wangjie Jiang, Xiangxu Kong, Xiao Zhou, Deming Zhu, Lianbao Kong
Summary: Genistein can upregulate miR-1275 expression and inhibit the epithelial mesenchymal transformation (EMT) and stemness of hepatocellular carcinoma (HCC). MiR-1275 inhibits EMT and stemness of HCC by suppressing the EIF5A2/PI3K/Akt pathway.
Article
Biochemistry & Molecular Biology
Vojtech Pavlik, Veronika Machalova, Martin Cepa, Romana Sinova, Barbora Safrankova, Jaromir Kulhanek, Tomas Drmota, Lukas Kubala, Gloria Huerta-Angeles, Vladimir Velebny, Kristina Nesporova
Summary: The study found that HA-atRA upregulated gene expression similarly to atRA, but HA-atRA activated the expression of cholesterol metabolism genes. The results showed that HA-atRA removed cholesterol from the cells and induced cholesterol synthesis to replenish it. Additionally, HA-C18:1 also removed cholesterol from the cells, indicating that the cholesterol removal stemmed from the amphiphilic nature of these derivatives.
Review
Biotechnology & Applied Microbiology
Taja Zeleznik Ramuta, Tina Sket, Marjanca Starcic Erjavec, Mateja Erdani Kreft
Summary: The fetal membranes provide a supportive environment for the embryo and fetus and have gained attention for their antimicrobial properties in recent years. Antimicrobial peptides secreted by perinatal derivatives contribute to a healthy pregnancy and the prevention of complications. Research on the antimicrobial properties of fetal membranes and their derivatives has provided valuable insights for potential clinical applications, emphasizing the importance of standardization in preparation, testing methods, in vivo studies, and donor selection criteria.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Gustavo Penteado Battesini Carretero, Greice Kelle Viegas Saraiva, Magali Aparecida Rodrigues, Sumika Kiyota, Marcelo Porto Bemquerer, Hernan Chaimovich, Iolanda Midea Cuccovia
Summary: Antimicrobial peptide BP100 demonstrates antibacterial activity, low toxicity, and increased membrane permeability. The fluorescent BP100 analogue NAPHT-BP100 interacts with cell membranes and DNA, showing stronger antibacterial and hemolytic activities compared to BP100, potentially making it an efficient antimicrobial agent for dermatological use.
Article
Multidisciplinary Sciences
Malwina A. Niechcial, Calum Marr, Lauren M. Potter, Adele Dickson, Alan J. Gow
Summary: This study explored the experiences and expectations of older adults who participated in a new activity. The findings identified both positive factors such as enjoyment and socialization, as well as negative factors such as lack of confidence, other commitments, class costs, and poor structure. Future research should also consider addressing barriers for those who are not readily participating in leisure activities.
Article
Cell Biology
Qian Zhong, Yixin Liu, Michele Ramos Correa, Crystal Nicole Marconett, Parviz Minoo, Changgong Li, David K. Ann, Beiyun Zhou, Zea Borok
Summary: NKX2.1 and FOXO1 have significant interactions in regulating specific gene expression and cell fate in the distal lung, with FOXO1 playing a central role in alveolar epithelial cell differentiation and maintaining homeostasis.
Article
Polymer Science
Morena Petrini, Emira D'Amico, Tania Vanessa Pierfelice, Gitana Maria Aceto, Maryia Karaban, Pietro Felice, Adriano Piattelli, Antonio Barone, Giovanna Iezzi
Summary: This study aimed to test the effectiveness of a photodynamic protocol involving a gel with aminolevulinic acid and red LED irradiation (ALAD-PDT) on human gingival fibroblasts (hGFs) and osteoblasts (hOBs) cultured on a porcine acellular dermal matrix membrane (PADMM). Results showed that ALAD-PDT promoted cellular induction, forming a dense cellular network, with significantly higher values compared to LED alone and the control group.
Review
Biochemistry & Molecular Biology
Ronja Reinhardt, Linda Truebestein, Heiko A. Schmidt, Thomas A. Leonard
Review
Biochemistry & Molecular Biology
Ivan Yudushkin
Article
Multidisciplinary Sciences
Sara Sajko, Irina Grishkovskaya, Julius Kostan, Melissa Graewert, Kim Setiawan, Linda Truebestein, Korbinian Niedermueller, Charlotte Gehin, Antonio Sponga, Martin Puchinger, Anne-Claude Gavin, Thomas A. Leonard, Dimitri I. Svergun, Terry K. Smith, Brooke Morriswood, Kristina Djinovic-Carugo
Article
Biochemistry & Molecular Biology
Daniel Pokorny, Linda Truebestein, Kaelin D. Fleming, John E. Burke, Thomas A. Leonard
Summary: The activation of Sgk3 is regulated by phosphatidylinositol 3-phosphate (PI3P) downstream of growth factor signaling via class I phosphatidylinositol 3-kinase (PI3K) signaling and by class III PI3K/Vps34-mediated PI3P production on endosomes. This activation is controlled by a combination of phosphorylation and allosteric activation, with PI3P inducing conformational changes in Sgk3 via its PX domain, leading to activation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Linda Truebestein, Harald Hornegger, Dorothea Anrather, Markus Hartl, Kaelin D. Fleming, Jordan T. B. Stariha, Els Pardon, Jan Steyaert, John E. Burke, Thomas A. Leonard
Summary: The study reveals the crystal structure of Akt1 and its autoinhibitory interface between PH and kinase domains, shedding light on the regulation of its activity by lipids and phosphorylation. This has significant implications for the spatiotemporal control of Akt and potential lipid-activated kinase signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Mouhannad Malek, Anna M. Wawrzyniak, Michael Ebner, Dmytro Puchkov, Volker Haucke
Summary: This study reveals a mechanism for controlling lysosome biogenesis involving calcium release from the endoplasmic reticulum, independent of mechanistic target of rapamycin complex 1. The mechanism includes inositol polyphosphate-5-phosphatase A-mediated triphosphate hydrolysis, calcineurin, and the nuclear translocation and elevated transcriptional activity of TFEB/TFE3.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Aleksandra Levina, Kaelin D. Fleming, John E. Burke, Thomas A. Leonard
Summary: This study elucidates the mechanism of self-activation of 3-phosphoinositide-dependent kinase 1 (PDK1). It is activated by dimerization mediated by PIP3 and trans-autophosphorylation, while its PH domain inhibits its activity. These results suggest that phosphoinositide-dependent activation may also apply to various effector kinases.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Matthew C. Thibodeau, Noah J. Harris, Meredith L. Jenkins, Matthew A. H. Parson, John T. Evans, Mackenzie K. Scott, Alexandria L. Shaw, Daniel Pokorny, Thomas A. Leonard, John E. Burke
Summary: In this study, the researchers characterized the WDR44-Rab11 complex at a molecular level, identifying specific residues involved in binding and providing insights into how WDR44 interacts with Rab11 to regulate ciliogenesis. The findings also revealed the distinct dynamics of the WDR44-Rab11 interface compared to other Rab11 effectors, highlighting the specificity of WDR44 for Rab11 and its role in forming effector complexes that regulate membrane trafficking events.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Ronja Reinhardt, Kai Hirzel, Gisela Link, Stephan A. Eisler, Tanja Hagele, Matthew A. H. Parson, John E. Burke, Angelika Hausser, Thomas A. Leonard
Summary: Phosphorylation is a common mechanism in cell signaling, and protein kinases are often regulated by phosphorylation. However, PKD regulates itself through dimerization-mediated trans-autoinhibition, followed by autophosphorylation, to control its activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Linda Truebestein, Sumire Antonioli, Elisabeth Waltenberger, Charlotte Gehin, Anne -Claude Gavin, Thomas A. Leonard
Summary: Protein kinases of the DMPK family are crucial for actomyosin contractility. MRCK1, a DMPK kinase, is necessary for myosin activation, which leads to cortical tension, apical constriction, and early gastrulation. This study provides insights into the structure, conformation, and membrane-binding properties of Caenorhabditis elegans MRCK1. It reveals a homodimer structure of MRCK1, consisting of N-terminal kinase domains, a coiled coil, and a C-terminal module with C1, PH, and CNH domains. The study also investigates the interaction between the CRIB motif and Cdc42 and suggests that the coiled-coil domain may function as a molecular ruler for kinase activity.
Article
Biochemistry & Molecular Biology
Alexandria L. Shaw, Matthew A. H. Parson, Linda Truebestein, Meredith L. Jenkins, Thomas A. Leonard, John E. Burke
Summary: Akt is a key regulator of cell growth signaling and its hyperactivation is oncogenic. This study used hydrogen deuterium exchange mass spectrometry to investigate the conformational changes induced by Akt inhibitors. The findings provide valuable insights for designing targeted therapeutics against Akt.
Review
Biochemical Research Methods
Christopher Schmied, Michael S. Nelson, Sergiy Avilov, Gert-Jan Bakker, Cristina Bertocchi, Johanna Bischof, Ulrike Boehm, Jan Brocher, Mariana T. Carvalho, Catalin Chiritescu, Jana Christopher, Beth A. Cimini, Eduardo Conde-Sousa, Michael Ebner, Rupert Ecker, Kevin Eliceiri, Julia Fernandez-Rodriguez, Nathalie Gaudreault, Laurent Gelman, David Grunwald, Tingting Gu, Nadia Halidi, Mathias Hammer, Matthew Hartley, Marie Held, Florian Jug, Varun Kapoor, Ayse Aslihan Koksoy, Judith Lacoste, Sylvia Le Devedec, Sylvie Le Guyader, Penghuan Liu, Gabriel G. Martins, Aastha Mathur, Kota Miura, Paula Montero Llopis, Roland Nitschke, Alison North, Adam C. Parslow, Alex Payne-Dwyer, Laure Plantard, Rizwan Ali, Britta Schroth-Diez, Lucas Schuetz, Ryan T. Scott, Arne Seitz, Olaf Selchow, Ved P. Sharma, Martin Spitaler, Sathya Srinivasan, Caterina Strambio-De-Castillia, Douglas Taatjes, Christian Tischer, Helena Klara Jambor
Summary: This article presents community-developed checklists for preparing light microscopy images and describing image analyses in order to enhance the clarity and reproducibility of image figures and improve the quality and explanatory power of microscopy data.
Article
Biochemistry & Molecular Biology
Iva Lucic, Pin-Lian Jiang, Andreas Franz, Yuval Bursztyn, Fan Liu, Andrew J. R. Plested
Summary: Using unnatural amino acid mutagenesis, a mutant of CaMKII was created that can form a covalent linkage to Calmodulin upon UV light illumination. The binding of Calmodulin to this mutant does not perturb the oligomeric state of CaMKII, and it can be activated by UV-induced binding of Calmodulin in the absence of calcium. This mutant shows potential for controlling CaMKII activity with light.
Review
Biology
Ronja Reinhardt, Thomas A. Leonard
Summary: Phosphorylation of proteins is a common mechanism for regulating their function, localization, or activity. Protein kinases, which use ATP to phosphorylate protein substrates, are important signal transducers in cells. The mechanism of phosphoryl-transfer is conserved among protein kinases, and the precise mechanism of autophosphorylation is still a topic of debate. In this review, we evaluate different proposed mechanisms of autoregulation in protein kinases and discuss their implications in physiological signaling networks.
Article
Biology
Iva Lucic, Leonie Heluin, Pin-Lian Jiang, Alejandro G. Castro Scalise, Cong Wang, Andreas Franz, Florian Heyd, Markus C. Wahl, Fan Liu, Andrew J. R. Plested
Summary: The dodecameric protein kinase CaMKII is expressed throughout the body and plays a crucial role in synaptic plasticity and memory. Contrary to previous expectations, our study reveals that subunit exchange is not the main mechanism for the spread of CaMKII activity. Instead, inter-holoenzyme phosphorylation (IHP) is identified as the mechanism for spreading phosphorylation.