Article
Multidisciplinary Sciences
Alex J. Vecchio, Sewwandi S. Rathnayake, Robert M. Stroud
Summary: The study reveals the molecular and structural basis of how CpE targets susceptible claudins, as well as differences in the primary CpE receptors in mice and humans due to sequence changes in the target motif.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
Amita R. Banga, Peace Odiase, Kartik Rachakonda, Amar P. Garg, Samuel E. Adunyah, Girish Rachakonda
Summary: This article discusses the potential value of the interaction between Clostridium perfringens Enterotoxin (CPE) and Claudin-4 in the treatment of breast cancer metastasis to the brain, and introduces the important role of Claudin-4 in cell trafficking and disease development.
Article
Multidisciplinary Sciences
Nandhini Rajagopal, Shikha Nangia
Summary: This study investigates the molecular assembly of claudins, specifically claudin-5 and claudin-15, to determine their structural and functional properties. The research findings suggest that each member of the claudin family has a unique strand architecture that requires systematic molecular-level analysis.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Review
Cell Biology
Chinemerem P. Ogbu, Sourav Roy, Alex J. Vecchio
Summary: Claudins are integral membrane proteins that play a crucial role in cell-cell interactions by forming tight junctions. The bacterium Clostridium perfringens causes gastrointestinal disorders by targeting claudins with its enterotoxin (CpE), disrupting the barrier function of the gut. Understanding the structure and function of Claudin and CpE provides insights into the mechanisms underlying the disruption of tight junctions. This review summarizes the current progress in this field and highlights the importance of structural studies in developing therapeutic strategies.
Article
Pharmacology & Pharmacy
Ayk Waldow, Laura-Sophie Beier, Janine Arndt, Simon Schallenberg, Claudia Vollbrecht, Philip Bischoff, Marti Farrera-Sal, Florian N. Loch, Christian Bojarski, Michael Schumann, Lars Winkler, Carsten Kamphues, Lukas Ehlen, Joerg Piontek
Summary: Claudins regulate paracellular permeability, contribute to epithelial polarization and are dysregulated during inflammation and carcinogenesis. Variants of the claudin-binding domain of Clostridium perfringens enterotoxin (cCPE) are highly sensitive protein ligands for generic detection of a broad spectrum of claudins. This study used cCPE fusion proteins to specifically and efficiently detect claudin expression, localization and tight junction dysregulation in various models of gastrointestinal epithelia.
Article
Biochemistry & Molecular Biology
Panpan Lin, Rongbang Tan, Ping Yu, Yanyu Li, Yuqian Mo, Wen Li, Jingjing Zhang
Summary: The blood-brain barrier is essential for protecting the central nervous system, but it also hinders efficient drug delivery. This study demonstrates that a mutated fragment of Clostridium perfringens enterotoxin can regulate the dynamics of the endothelial tight junction protein claudin-5 and influence blood-brain barrier permeability.
Article
Multidisciplinary Sciences
Ruixue Xia, Na Wang, Zhenmei Xu, Yang Lu, Jing Song, Anqi Zhang, Changyou Guo, Yuanzheng He
Summary: The authors used cryo-EM to determine the complex structure of histamine-bound H1R/Gq and proposed a mechanism for ligand-induced receptor activation, providing insights for designing novel antihistamines.
NATURE COMMUNICATIONS
(2021)
Article
Dentistry, Oral Surgery & Medicine
Qing-Ting Yao, Yan-Hui Wu, Shao-Hua Liu, Xiao-Bin Song, Hui Xu, Jun Li, Liang Shi
Summary: The study investigated the effects of radiation on rat submandibular glands and the mechanisms of increased secretion following pilocarpine treatment. It was found that pilocarpine could improve the secretory function of irradiated rat submandibular glands by reducing inflammation, ameliorating the structural injury of tight junctions, and attenuating the up-regulation of claudin-4 expression.
Article
Chemistry, Multidisciplinary
Li Li Tian, Chun Hong Li, Qi Chao Ye, Yuan Fang Li, Cheng Zhi Huang, Lei Zhan, Dong Mei Wang, Shu Jun Zhen
Summary: A centrifugal microfluidic chip-based strategy for point-of-care testing of Staphylococcal enterotoxin B (SEB) was proposed, utilizing an immune sandwich structure. The method allows for detection of SEB within 12 minutes, with good stability and a low limit of detection.
Article
Multidisciplinary Sciences
Defen Lu, Guijun Shang, Xiaojing He, Xiao-chen Bai, Xuewu Zhang
Summary: This study presents the cryo-EM structure of the extracellular Sema3A/PlexinA4/Neuropilin1 complex, providing further insights into the interactions among semaphorin, plexin and neuropilin, and revealing the importance of long flexible linkers in semaphorin and neuropilin for complex formation.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Yuxia Qian, Jiening Wang, Linlin Yang, Yanru Liu, Lina Wang, Wei Liu, Yun Lin, Hong Yang, Lixin Ma, Sheng Ye, Shan Wu, Anna Qiao
Summary: This study reveals that GPR119 adopts a non-canonical consensus structural scaffold and possesses an extended ligand-binding pocket for chemically different agonists.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Megan R. Beggs, Kennedi Young, Wanling Pan, Debbie D. O'Neill, Matthew Saurette, Allein Plain, Juraj Rievaj, Michael R. Doschak, Emmanuelle Cordat, Henrik Dimke, R. Todd Alexander
Summary: Calcium homeostasis is maintained through coordination between intestinal absorption, renal reabsorption, and bone remodeling with tight-junction proteins called claudins playing a crucial role. Claudins-2 and -12 form independent Ca2+ permeable pores in renal and colonic epithelia, with either one sufficient to maintain Ca2+ balance. Deletion of both claudins leads to reduced intestinal Ca2+ absorption, higher urinary Ca2+ wasting, hypocalcemia, and reduced bone mineral density compared to single-null animals.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Microbiology
Clayton M. Carey, Sarah E. Apple, Zoe A. Hilbert, Michael S. Kay, Nels C. Elde
Summary: The study found that mammals exhibit species-specific resistance to diarrheal pathogens, particularly in primates and bats. The diversification of the intestinal receptor GC-C in bats can lead to compensatory mutations in the endogenous ligand, suggesting that pathogens may have driven the evolution of this signaling axis to some extent.
CELL HOST & MICROBE
(2021)
Review
Endocrinology & Metabolism
Philipp Y. Maximov, Ping Fan, Balkees Abderrahman, Ramona Curpan, V. Craig Jordan
Summary: Antiestrogen therapy is the standard treatment for estrogen receptor-positive breast cancer, but resistance can develop. Recent studies have found that long-term estrogen deprived breast cancer cells may undergo apoptosis in response to estrogen treatment. This review provides an overview of the structure-activity relationship of different estrogens and their modulation of estrogen-induced apoptosis in LTED breast cancer cells.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Oncology
Chen Wang, Na Wu, Beibei Pei, Xiaoyan Ma, Wenhui Yang
Summary: Due to lack of timely and accurate screening methods and treatments, pancreatic cancer patients often experience rapid disease progression. The claudin family, specifically expressed in tight junctions of various tumors including pancreatic cancer, can affect tumor progression by altering cell junctions. Some members of the claudin family, such as claudin-18.2 and claudin-4, are significantly dysregulated in pancreatic tumors and have been implicated in diagnosis and treatment. Different targets of claudin proteins, combined with chemotherapy, can enhance tumor cell necrosis and inhibit invasion and metastasis. This literature review focuses on the functional characteristics and clinical applications of claudin proteins in pancreatic cancer cells, with particular attention to claudin-18.2 and claudin-4.
FRONTIERS IN ONCOLOGY
(2023)
Review
Cell Biology
Emmanuel Lemichez, Michel Robert Popoff, Karla J. F. Satchell
CELLULAR MICROBIOLOGY
(2020)
Review
Cell Biology
Carolina Varela-Chavez, Arnaud Blondel, Michel R. Popoff
CELLULAR MICROBIOLOGY
(2020)
Review
Food Science & Technology
Christine Rasetti-Escargueil, Emmanuel Lemichez, Michel R. Popoff
Review
Food Science & Technology
Christine Rasetti-Escargueil, Michel R. Popoff
Summary: Botulinum neurotoxins (BoNTs) have increasingly diverse therapeutic applications, ranging from treating muscle and neurological disorders such as muscle hyperactivity, essential tremor, and movement disorders. Advances in molecular biology have led to the development of modified BoNTs with potential for treating a variety of disorders.
Article
Multidisciplinary Sciences
Holger Bruggemann, Diana Chapeton-Montes, Lucile Plourde, Michel R. Popoff
Summary: Research revealed that Clostridium tetani may regulate the synthesis of tetanus toxin through a putative non-coding small RNA, potentially impacting bacterial growth and preventing premature bacterial lysis.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Sebastien Brier, Christine Rasetti-Escargueil, Anne Wijkhuisen, Stephanie Simon, Maud Marechal, Emmanuel Lemichez, Michel R. Popoff
Summary: The study identified the unique neutralization mechanism of TA12, demonstrating that its conformational epitope recognizes the specific region at the interface of the BoNT/A1 receptor-binding domain and overlaps with the binding site for the neuronal cell surface receptors SV2C and GT1b. TA12 effectively blocks the entry of BoNT/A1 into neurons by interfering with the binding of SV2C and, to a lesser extent, GT1b, highlighting the potential of using single mAbs for the treatment of botulism type A.
Editorial Material
Food Science & Technology
Daniel Ladant, Pascale Marchot, Sylvie Diochot, Gilles Prevost, Michel R. Popoff, Evelyne Benoit
Summary: This report presents the 27th annual meeting of the French Society of Toxinology, which focused on the dual nature of toxins and showcased the latest research findings on plant, fungal, algal, animal, and bacterial toxins.
Review
Food Science & Technology
Michel R. Popoff, Holger Bruggemann
Summary: Clostridium botulinum and Clostridium tetani are bacteria that produce potent neurotoxins and cause paralysis. The synthesis of neurotoxins is regulated by complex networks involving environmental factors, nutrition, and regulatory pathways.
Review
Microbiology
Christine Rasetti-Escargueil, Michel R. Popoff
Summary: Botulinum neurotoxins are protein complexes produced by bacteria of the genus Clostridium. There is a need for fast, accurate, and reliable detection methods to monitor botulism outbreaks and for therapeutic and research purposes. Current methods include immunological and mass spectrometry approaches, but further validation is required. Cell-based assays have the potential to replace animal testing for potency determination and inhibitor identification, but their development still requires in vivo studies.
Article
Food Science & Technology
Grazia Cottone, Letizia Chiodo, Luca Maragliano, Michel-Robert Popoff, Christine Rasetti-Escargueil, Emmanuel Lemichez, Therese E. Malliavin
Summary: Combined homology modeling and atomistic simulations are used to investigate the internal dynamics of botulinum neurotoxins (BoNTs). The study reveals that the conformational variations of BoNTs are influenced by pH and protein structure, and the mobility of the belt alpha-helix may interact with the core translocation domain during the translocation process, providing important insights into the molecular mechanism of BoNTs.
Review
Food Science & Technology
Michel R. R. Popoff, Sandra Legout
Summary: Louis Pasteur, a pioneer in microbiology, discovered anaerobic life and identified the first pathogenic anaerobic bacterium. He focused on the prevention and treatment of infectious diseases using attenuated pathogens. His collaborators investigated the mechanisms of pathogenicity and found that bacterial toxins induce symptoms and lesions in experimental animals.
Article
Cell Biology
Daria Chirita, Pauline Bronnec, Flora Magnotti, Sarah Dalmon, Amandine Martin, Michel Popoff, Mathieu Gerfaud-Valentin, Pascal Seve, Alexandre Belot, Anne Contis, Agnes Duquesne, Gaetane Nocturne, Irene Lemelle, Sophie Georgin-Lavialle, Guilaine Boursier, Isabelle Touitou, Yvan Jamilloux, Thomas Henry
Summary: This study reveals the role of the B30.2 domain and the central helical scaffold (CHS) domain in regulating pyrin inflammasome activation in Familial Mediterranean Fever (FMF). Mutations in these domains can have different functional impacts on the pyrin inflammasome, contributing to the diversity of pyrin-associated autoinflammatory diseases.
CELL DEATH & DISEASE
(2023)
Editorial Material
Food Science & Technology
Daniel Ladant, Gilles Prevost, Michel R. Popoff, Evelyne Benoit
Review
Food Science & Technology
Michel R. R. Popoff, Grazyna Faure, Sandra Legout, Daniel Ladant
Summary: Humans have encountered poisonous animals since ancient times. Certain animals and plants produce toxic substances that can be deadly or have medicinal effects. The term venom now refers specifically to poisons delivered by biting. Scientists from the Institut Pasteur in Paris pioneered the development of antivenom therapy, paving the way for research on venom constituents and their biological activities. The study of snake venoms conducted by scientists at the Institut Pasteur has greatly contributed to the field.
Meeting Abstract
Pharmacology & Pharmacy
S. Worbs, B. Kampa, M. Skiba, K. Busschots, R. Zeleny, J. Masquelier, A. Puustinen, P. Vanninen, C. Rasetti-Escargueil, M. Popoff, E. Lemichez, A. S. Mierzala, H. Volland, F. Becher, S. Simon, B. Boran, Y. Nia, J. A. Hennekinne, J. Weisemann, A. Rummel, D. Jansson, M. A. Avondet, W. Luginbuhl, R. Josuran, C. Zaborosch, L. Burns, K. Campbell, B. Dorner
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)