A novel pathological mutant reveals the role of torsional flexibility in the serpin breach in adoption of an aggregation‐prone intermediate
The FEBS Journal
by Kamila Kamuda, Riccardo Ronzoni, Avik Majumdar, Fiona H. X. Guan, James A. Irving, David A. Lomas
3d ago
Here, we characterised a novel pathological variant of alpha-1-antitrypsin with a single substitution of glycine to cysteine at position 192. This mutation is positioned within the breach region, which is crucial for inhibitory function of the protein. Glycine substitution leads to reduced flexibility within the breach region, alters protein activity and leads to alpha-1-antitrypsin polymer accumulation within the cell. Mutants of alpha-1-antitrypsin cause the protein to self-associate and form ordered aggregates (‘polymers’) that are retained within hepatocytes, resulting in a predispositio ..read more
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A guide to germ‐free and gnotobiotic mouse technology to study health and disease
The FEBS Journal
by Maude Jans, Lars Vereecke
3d ago
Germ-free and gnotobiotic mouse technology allows the unraveling of complex host–microbiota interactions within a reductionist framework. The implementation of these methodologies poses significant technical and experimental challenges. This review explores practical insights aimed at enhancing the precision and success of germ-free and gnotobiotic experiments. The intestinal microbiota has major influence on human physiology and modulates health and disease. Complex host–microbe interactions regulate various homeostatic processes, including metabolism and immune function, while disturbances ..read more
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A biological guide to glycosaminoglycans: current perspectives and pending questions
The FEBS Journal
by Sylvie Ricard‐Blum, Romain R. Vivès, Liliana Schaefer, Martin Götte, Rosetta Merline, Alberto Passi, Paraskevi Heldin, Ana Magalhães, Celso A. Reis, Spyros S. Skandalis, Nikos K. Karamanos, Serge Perez, Dragana Nikitovic
1w ago
Mammalian glycosaminoglycans, except hyaluronan, are sulfated polysaccharides that are covalently attached to core proteins to form proteoglycans. They contribute to the organization of the extracellular matrix and are displayed at the cell surface where they regulate the availability and activity of cytokines and growth factors and cell signaling. Their biosynthesis is altered in cancer, inflammation, and fibrosis, making them potential biomarkers of these diseases. Mammalian glycosaminoglycans (GAGs), except hyaluronan (HA), are sulfated polysaccharides that are covalently attached to core ..read more
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Salmonella‐driven intestinal edema in mice is characterized by tensed fibronectin fibers
The FEBS Journal
by Ronja Rappold, Konstantinos Kalogeropoulos, Ulrich auf dem Keller, Viola Vogel, Emma Slack
1w ago
Salmonella-induced intestinal inflammation elicits diverse tissue morphology alterations, notably submucosal edema formation through fluid accumulation in the interstitial space. Our study underscores the significance of extracellular matrix components in preserving tissue integrity during acute inflammation. We observe stretched fibronectin fibers proximal to fibrin(ogen), contrasting with a disrupted collagen network. We propose a pivotal role for tensed fibronectin fibers in upholding tissue integrity, suggesting potential protective mechanisms against proteolytic cleavage. Intestinal ede ..read more
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Issue Information
The FEBS Journal
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2w ago
Cover Illustration TcHRG orchestrates heme uptake in Trypanosoma cruzi epimastigotes. Image provided by Julia Alejandra Cricco and colleagues, authors of the Original Article included in this issue, pages 1186–1198 ..read more
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Genetic and epigenetic dysregulation of innate immune mechanisms in autoinflammatory diseases
The FEBS Journal
by Laura M. Merlo Pich, Athanasios Ziogas, Mihai G. Netea
2w ago
Dysregulation and hyperactivation of innate immune responses can lead to the onset of systemic autoinflammatory diseases, caused by inborn genetic errors alone, or in combination with non-genetic factors. Innate immune memory (trained immunity) is physiologically beneficial, but can become maladaptive, perpetuating chronic inflammatory activation. Here, we describe the mechanisms of genetic and epigenetic dysregulation of the innate immune system and maladaptive trained immunity leading to the onset of systemic autoinflammatory diseases. Dysregulation and hyperactivation of innate immune res ..read more
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Isolation of an H2‐dependent electron‐bifurcating CO2‐reducing megacomplex with MvhB polyferredoxin from Methanothermobacter marburgensis
The FEBS Journal
by Shunsuke Nomura, Nicole Paczia, Jörg Kahnt, Seigo Shima
2w ago
Here, we report the isolation and characterization of a 1-MDa complex of formylmethanofuran dehydrogenase (Fmd), heterodisulfide reductase (Hdr), and Hdr-associating [NiFe] hydrogenase (Mvh) from Methanothermobacter marburgensis. The megacomplex contained a polyferredoxin subunit, MvhB. The Mvh-Hdr-Fmd megacomplex catalyzed the electron-bifurcating reduction of CO2 to form formyl-methanofuran in the absence of extrinsic ferredoxin, demonstrating that the megacomplex is electronically linked and that MvhB likely functions as an electron relay. In the hydrogenotrophic methanogenic pathway, for ..read more
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ADGRG1, an adhesion G protein‐coupled receptor, forms oligomers
The FEBS Journal
by Orkun Cevheroğlu, Berkay Demirbaş, Dilara Öğütcü, Merve Murat
2w ago
ADGRG1, an adhesion G protein-coupled receptor, forms homo-oligomers driven by 7-transmembrane interactions on the plasma membrane. Moreover, Stachel interactions with the receptor 7-transmembrane domain appear to impact the conformation of these oligomeric complexes, providing initial insights into the homo-oligomerization of adhesion G protein-coupled receptors. G protein-coupled receptor (GPCR) oligomerization is a highly debated topic in the field. While initially believed to function as monomers, current literature increasingly suggests that these cell surface receptors, spanning almost ..read more
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Study of an FBXO7 patient mutation reveals Fbxo7 and PI31 co‐regulate proteasomes and mitochondria
The FEBS Journal
by Sara Al Rawi, Lorna Simpson, Guðrún Agnarsdóttir, Neil Q. McDonald, Veronika Chernuha, Orly Elpeleg, Massimo Zeviani, Roger A. Barker, Ronen Spiegel, Heike Laman
2w ago
A mutation identified in an infant maps to the dimerisation domain of the Parkinson's disease-associated gene, FBXO7/PARK15, and prevents its interaction with a proteasome regulator, PI31. We characterised the patient's fibroblasts and found multiple deficiencies in proteasome activity and mitochondrial function. Unexpectedly, we found that the activity of the Fbxo7 L250P ubiquitin ligase was decreased towards some of its substrates. Furthermore, the patient's cells showed reduced viability to specific stress conditions. Mutations in FBXO7 have been discovered to be associated with an atypic ..read more
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Upregulated expression of lamin B receptor increases cell proliferation and suppresses genomic instability: implications for cellular immortalization
The FEBS Journal
by Atsuki En, Kentaro Takemoto, Yoshimi Yamakami, Kazuhiko Nakabayashi, Michihiko Fujii
2w ago
Normal somatic cells undergo cellular senescence; however, cells can acquire the ability to proliferate infinitely (immortalization) through multiple genetic alterations. Simian virus 40 large T antigen (TAg), which inactivates p53 and RB, facilitates cellular immortalization. Lamin B receptor (LBR), which regulates heterochromatin organization, is downregulated in senescent cells but upregulated in immortalized cells. Upregulated LBR expression increases proliferation of TAg-expressing cells through suppression of genomic instability, and plays a crucial role in the process of cellular immor ..read more
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