Article
Biochemical Research Methods
Zhen Xu, Saif Khan, Nicholas J. Schnicker, Sheila Baker
Summary: This study used X-ray crystallography to determine the structure of the human Kv2.1 T1 domain and found that it forms a pentamer, different from other Kv T1 domains. The study also demonstrated the importance of zinc binding for the stability of the Kv2.1 T1 domain.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jordi Gomez Borrego, Marc Torrent Burgas
Summary: Adhesion and colonization of host cells by pathogenic bacteria rely on protein-protein interactions (PPIs). This study developed a filtering process to obtain a reliable list of domains and motifs participating in PPIs between bacteria and human cells. Structural analysis revealed that human proteins involved in these interactions are rich in alpha helix and disordered regions. The most significant domain-domain interactions were validated, but verifying domain-motif interactions was more challenging. Post-translational modifications, especially phosphorylation, also play a role in these interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jeffry C. Nichols, Celia A. Schiffer, William E. Royer
Summary: Research has shown that ADP and AMP in NAD(H) are crucial in promoting tetramer formation of CtBP1 and CtBP2, while other parts lacking adenosine phosphate are unable to promote tetramer assembly. Structural studies have highlighted the central role of adenosine phosphate in NAD(H)-linked assembly, and the overlapping yet unique functions of CtBP1 and CtBP2 suggest that a detailed understanding of their structural properties could be beneficial in designing paralog-specific inhibitors.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Kyoko Okada, Bharat R. Iyer, Lindsay G. Lammers, Pedro A. Gutierrez, Wenzhe Li, Steven M. Markus, Richard J. Mckenney
Summary: This study reveals previously unknown steps in the activation pathway of cytoplasmic dynein-mediated cargo transport and provides insight into the integrated activities of LIS1/Ndel1 and dynactin/cargo-adapters. The findings contribute to the understanding of the roles of the human disease genes Ndel1 and LIS1 in the assembly and activation of dynein transport complexes.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
James H. Baraniak, Yandong Zhou, Robert M. Nwokonko, Michelle R. Jennette, Sarah A. Kazzaz, Jazmin M. Stenson, Abigale L. Whitsell, Youjun Wang, Mohamed Trebak, Donald L. Gill
Summary: The study reveals that the interaction between M4x peptides in Orai channels and STIM1 protein can block Ca2+ signal transduction and affect the coupling between STIM and Orai proteins, thereby regulating the cell's Ca2+ signaling pathway.
Article
Biochemistry & Molecular Biology
Elizabeth Vargas, Kenneth E. Prehoda
Summary: The Par complex polarizes animal cells through multiple regulators. The transition from Par-3 to Cdc42 is a critical step in Par-mediated polarity, but little is known about how it occurs. This study reveals that Par-3 and Cdc42 exhibit negative cooperativity for the Par complex and identifies the minimal components required for this transition to occur. These findings provide insights into the regulation of Par complex polarization and activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Vladislav M. Shatov, Nikolai N. Sluchanko, Nikolai B. Gusev
Summary: The study analyzed the impact of mutations in the highly conservative sequence located in the N-terminal domain of human HspB8 on its physico-chemical properties and chaperone-like activity. Mutations were found to affect the oligomeric structure and key properties of HspB8, with the R29A substitution leading to predominant formation of oligomers and the deletion of the pentapeptide resulting in the formation of dimers. Additionally, the study revealed that the R29A mutation weakly bound a hydrophobic probe and resisted chymotrypsinolysis, affecting the chaperone-like activity of HspB8.
Article
Biophysics
Koushik Choudhury, Marina A. Kasimova, Sarah McComas, Rebecca J. Howard, Lucie Delemotte
Summary: This study used molecular modeling and simulations to test possible open-state models of NavMs channels from the bacterium Magnetococcus marinus, finding that the experimental structure was unable to conduct ions at the activation gate. By observing a spontaneous transition and comparing with other Nav channels, an alternative stable open-state model was built, showing consistent pore hydration, ion permeation, and drug binding with the functional open state.
BIOPHYSICAL JOURNAL
(2022)
Article
Cell Biology
Christian de Groot, Jack Houston, Bethany Davis, Adina Gerson-Gurwitz, Joost Monen, Pablo Lara-Gonzalez, Karen Oegema, Andrew K. Shiau, Arshad Desai
Summary: The extended N-terminal tail of CENP-A in Caenorhabditis elegans plays a crucial role in kinetochore assembly and chromosome condensation by interacting directly with KNL-2 protein. Results demonstrate that the N-terminal tail of CENP-A contains a structured region predicted to be essential for centromeric chromatin assembly, highlighting an evolutionary variation in centromere structure and function in the absence of a specific CENP-A chaperone/targeting factor.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Cell Biology
Thomas Torng, William Wickner
Summary: Intracellular membrane fusion requires a combination of specific lipids such as phosphatidylinositol and phosphatidylinositol-3-phosphate for HOPS activation and other lipids like phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, and diacylglycerol for the terminal bilayer rearrangement step of fusion. Different lipid requirements are crucial for activating HOPS for trans-SNARE assembly and for the final fusion process.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Cell Biology
Bram Van den Broek, Charlotte Wuyts, Angela Sisto, Isabel Pintelon, Jean-Pierre Timmermans, Veerle Somers, Vincent Timmerman, Niels Hellings, Joy Irobi
Summary: This study demonstrates that HSPB8-enriched oligodendroglia secreted EVs have a supportive role comparable to native OL-EVs, functioning in controlling chronic inflammation and maintaining cellular homeostasis.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Oncology
Spela Gubic, Louise Antonia Hendrickx, Xiaoyi Shi, Zan Toplak, Stefan Mozina, Kenny M. Van Theemsche, Ernesto Lopes Pinheiro-Junior, Steve Peigneur, Alain J. Labro, Luis A. Pardo, Jan Tytgat, Tihomir Tomasic, Lucija Peterlin Masic
Summary: In this article, a new class of potassium channel inhibitors is described, which selectively inhibits the K(V)1.3 channel and shows potential in inducing apoptosis and inhibiting cell proliferation. The K(V)1.3 channel has recently emerged as a target in cancer therapy. Through structural optimization, a novel K(V)1.3 inhibitor was designed and its potency and selectivity were investigated. The results showed that the new K(V)1.3 inhibitors effectively inhibited cancer cell proliferation and induced apoptosis.
Article
Biochemistry & Molecular Biology
Costanza E. Maurici, Robin Colenbier, Britta Wylleman, Luigi Brancato, Eke van Zwol, Johan Van den Bossche, Jean-Pierre Timmermans, Elisa Giovannetti, Marina G. M. C. Mori da Cunha, Johannes Bogers
Summary: The study found that hyperthermia not only directly inhibits the proliferation of PDAC cells, but also enhances the effectiveness of chemotherapy drugs, which has a positive impact on the treatment of PDAC patients.
Article
Anatomy & Morphology
Samuel Van Remoortel, Lana Lambeets, Jean-Pierre Timmermans
Summary: Mrgprs, a new family of Rhodopsin A-like G protein-coupled receptors, have been shown to play a critical role in itch, pain, and the inflammatory/allergic responses in the skin. Their role is not limited to the skin but extends to other mucosal surfaces. In the gastrointestinal tract, Mrgprs are emerging as novel sensory pathways associated with health and disease, closely linked to the gut's immune system.
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Laura Coonen, Evelyn Martinez-Morales, Dieter V. Van De Sande, Dirk J. Snyders, D. Marien Cortes, Luis G. Cuello, Alain J. Labro
Summary: This study found that the conductive state of the Shaker-IR-W434F-P475D mutant becomes loose and noncationic specific during the recovery from inactivation.
Article
Anatomy & Morphology
Jean-Pierre Timmermans
Summary: This article presents an introductory comment and overview of the autonomic nervous system research in Eastern Europe, with a focus on its innervation of the gastrointestinal tract and cardiovascular system. It also provides a selected overview of notable papers on these topics published in The Anatomical Record since 1906.
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
(2023)
Article
Chemistry, Medicinal
Szilvia Deri, Teodora Hartai, Laszlo Virag, Norbert Jost, Alain J. Labro, Andras Varro, Istvan Baczko, Stanley Nattel, Balazs Ordog
Summary: This study found that the candidate regulatory subunit KCNE3 of the I-Ks ion channel minimizes the inhibitory effects of LQT5 KCNE1 variants on I-Ks amplitudes and accelerates current deactivation. KCNE3 achieves this by displacing the KCNE1 subunit within the I-Ks ion channel complex.
Article
Anatomy & Morphology
Inge Brouns, Dirk Adriaensen, Jean-Pierre Timmermans
Summary: Exciting new imaging and molecular tools, combined with state-of-the-art genetically modified mouse models, have recently boosted interest in pulmonary (vagal) sensory pathway investigations. In addition, the review highlights the importance of studying the cellular and neuronal components of the pulmonary neuroepithelial bodies (NEBs) microenvironment (NEB ME) in mice, as it plays a crucial role in the mechano- and chemosensory potential of airways and lungs. Furthermore, the presence of different types of stem cells in the NEB ME and their potential role in lung pathogenesis or pathobiology is also discussed.
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
(2023)
Article
Cell Biology
Samuel Van Remoortel, Lana Lambeets, Heiko De Schepper, Jean-Pierre Timmermans
Summary: In recent years, it has been discovered that the family of Mas-related G protein-coupled receptors (MRGPRs) plays a crucial role in neuro-immune communication in the skin. However, the expression of MRGPRs at other mucosal surfaces remains poorly understood. This study aimed to investigate the expression of MRGPRs in mucosal biopsies of the human gastrointestinal (GI) tract. The results showed that MRGPRF mRNA was the only detectable member of the MRGPR family expressed in human mucosal biopsies of the terminal ileum and sigmoid colon. Immunohistochemical analysis revealed that MRGPRF was specifically expressed in mucosal entero-endocrine cells (EECs).
CELL AND TISSUE RESEARCH
(2023)
Article
Biology
Debby Van Dam, Femke Valkenburg, Kristof Van Kolen, Isabel Pintelon, Jean-Pierre Timmermans, Peter Paul De Deyn
Summary: The tau protein dysfunction is a core feature of neurodegenerative diseases, and mouse models expressing mutated tau protein associated with FTDP-17 can mimic some aspects of the disease. Our study demonstrates the validity of these models in replicating the pathology and symptoms of FTDP-17.
Article
Biochemistry & Molecular Biology
Kenny M. Van Theemsche, Joni G. Heymans, Nikola Z. Popovic, Evelyn Martinez-Morales, Dirk J. Snyders, Alain J. Labro
Summary: A cluster of charged residues at the top of S1 and the beginning of the S1-S2 linker are found to be close enough to S4 and offset (polarize) the electric field sensed by S4, contributing to the voltage dependence of channel activation.
Meeting Abstract
Biophysics
Laura Coonen, Evelyn Martinez-Morales, Luis G. Cuello, Dirk J. Snyders, Alain J. Labro
BIOPHYSICAL JOURNAL
(2022)
Article
Gastroenterology & Hepatology
Denise van der Graaff, Shivani Chotkoe, Benedicte De Winter, Joris De Man, Christophe Casteleyn, Jean-Pierre Timmermans, Isabel Pintelon, Luisa Vonghia, Wilhelmus J. Kwanten, Sven Francque
Summary: In non-alcoholic fatty liver disease (NAFLD), hepatic blood flow is impaired and the blood pressure in the liver blood vessels is increased as a result of an increased response of the liver vasculature to vasoconstrictors. Using drugs to block the constriction of the intrahepatic vasculature, the resistance of the liver blood vessels decreases and the increased portal pressure is reduced. Moreover, blocking the vasoconstrictive endothelin-1 pathway restored parenchymal architecture and reduced disease severity.