The FEBS Journal

Our Disease Mechanisms Focus Issue is out now 📗🪰 Articles in this issue combine fundamental structural insight with mechanistic implications for disease. Read the issue here ➡️ febs.onlinelibrary.wiley.com/toc/17424658/2…

✂️ Have you heard of anti-CRISPR proteins? In our latest Issue 9, Lee and Park reveal the structural mechanisms behind how anti-CRISPR protein AcrIIA13b inhibits CRISPR–Cas9 function. This article is also accompanied by an insightful Commentary ✍ Tomas Šinkūnas, Giedre Tamulaitiene 📕 Investigating the molecular mechanisms underlying the anti-CRISPR function of AcrIIA13b protein 📖 Anti-CRISPR protein AcrIIA13b inhibits CRISPR–Cas9 function by preventing target DNA engagement. The Cas9–sgRNA ribonucleoprotein (RNP) normally recognizes the protospacer adjacent motif (PAM) duplex to initiate DNA cleavage. AcrIIA13b binding to the PAM-interacting WED–PI domain blocks this recognition, leaving the target DNA intact. This structural mechanism explains how AcrIIA13b suppresses Cas9-mediated genome interference and highlights its role as a molecular inhibitor of CRISPR–Cas9 activity. Discover the study, here ➡️ buff.ly/RFnBo0i ✍ So Yeon Lee, Hyun Ho Park Discover the Commentary article, here ➡️ buff.ly/USc4b6k #CRISPR #antiCRISPR #structuralbiology #ribonucleoprotein

💉 In this Viewpoint article, Kilic and Kocaefe discuss current therapeutic strategies for skeletal muscle dystrophies, focusing on fibrosis as a primary impediment to gene and regenerative medicine. They highlight the significant potential of fibrosis modulators in the development of next-generation therapies. 📕 Reframing fibrosis as a barrier to regeneration and gene delivery in muscular diseases 📖 Fibrosis impairs skeletal muscle function and regeneration by disrupting the satellite cell niche. Increased ECM stiffness reduces kinetic capacity, promoting atrophy alongside hindering the activation and migration of myoblasts required for regeneration. This fibrotic barrier blocks growth factors and gene therapy vectors from reaching their targets. Without addressing fibrosis, effective treatment of muscle degeneration remains unattainable. Discover the Viewpoint, here ➡️ buff.ly/TszvRLr ✍ Hasan Basri KILIÇ, Çetin Kocaefe #fibrosis #muscledegeneration #therapy #regeneration #skeletalmuscledystrophy

We have pusblished @DelaCruzLab1 a Commentary on a paper by Gao et al. in @FEBSJournal You can have a look following the link onlinelibrary.wiley.com/share/author/T…

🔦 We're delighted to highlight this brilliant study shedding light on a new mechanism in starvation-induced calcium signaling. 📕 A perilysosomal feedforward mechanism regulates starvation-induced calcium signaling 📖 When cells are starved of nutrients, they generate a starvation-induced calcium signal (SICS), however, its underlying mechanism was poorly understood. Giles et al. explored SICS components and their regulation by the Ca2+ sensor calmodulin (CaM). SICS was shown to involve sequential Ca2+ release from the lysosome and ER, followed by store-operated Ca2+ entry (SOCE). The calcium sensor calmodulin was identified to control the speed and strength of SICS by managing cytoplasmic Ca2+ clearance and a perilysosomal feedforward loop that boosts TRPML1 channel activity. Read the full study, here ➡️ buff.ly/Zsyhj0c ✍ Jennifer Giles, Abbie Sesker, Marcos Gonzalez, Abel Ferow, Elizabeth Danielle McConnaha, Quang-Kim Tran #starvation #calciumsignaling #perilysosome #TRPML1 #SICS

🧩 We invite you to discover our latest State-of-the-Art Review, which examines how cellular collaborations orchestrate tumour initiation and progression, framing the microenvironment not as a passive scaffold, but as the central architect of tumour behaviour. 📕 Beyond the chaos: How architecture structures tumour biology 📖 Tissue architecture shapes tumour initiation and progression through multiple interconnected layers continuously remodelled over time. This review outlines how physical forces, biochemical cues, cellular niches and systemic influences contribute to tumour evolution. We describe how these layers promote or restrain transformation during initiation within physiological architecture, how they change as tumours progress and how dynamic, multi-directional crosstalk between these layers guides cancer behaviour, offering a structured perspective on tumour complexity. Discover this excellent Review, here ➡️ buff.ly/aApPQ59 ✍ Lea Dörner, Catrin Lutz, Stefan Prekovic, Ph.D., Hendrik Messal #tissuearchitecture #cellularniche #tumourbiology #cancer #scaffold

🔔 Our Issue 9 is now online 🔔 In this new issue, dive into: 🔎State-of-the-Art Review discussing how tissue architecture shapes tumour biology 💪 A Viewpoint offering fresh insights into fibrosis within muscular diseases ✂️ A compelling study on anti-CRISPR protein AcrIIA13b, accompanied by a Commentary 🧬 An Editor's Choice article investigating how SARS-CoV-2 nucleocapsid protein variants have differential RNA chaperone activity ⭐️ Several original research studies spanning a diverse range of life-science topics Discover our new issue, here ➡️ buff.ly/VtdqUqc #tumourbiology #fibrosis #CRISPR #SARSCoV2 #CryoEM #HCC

🔓 Furthering our Focus Issue on Molecular Microbiology, we highlight a new study on visceral leishmaniasis. This research explores how Leishmania donovani PTP (homologous to human phosphatases of regenerating liver) and DUF21 (homologous to human cyclin M family) play a role in responding to changes in environmental magnesium levels and alter the parasite's survival. 📕 Leishmania donovani's protein tyrosine phosphatases interact with DUF21 and respond to environmental magnesium 📖 The Leishmania phosphatase PTP1, and possibly the genetically similar PTP2, interacts with the Leishmania transmembrane protein DUF21. When both ptp1 and ptp2 are knocked out of Leishmania (LdΔPTP1/2), the parasite can no longer survive without magnesium in vitro and has reduced viability in the host macrophage. Conversely, in duf21 knockout (LdΔDUF21), the parasite cannot survive in excessive magnesium in vitro but has a growth advantage in the host macrophage. Discover the study, here ➡️ buff.ly/Q3uHI8I ✍ Kayla Paulini, Hira Khursheed, Wen Wei Zhang, Isabelle Aubry, Greg Matlashewski, Michel L Tremblay, Patrick Lypaczewski, Ph.D. hashtag#Leishmania hashtag#parasite hashtag#magnesium hashtag#macrophage

🦟 While preventable and treatable, malaria remains a significant global health challenge. In our recent Molecular Microbiology Focus Issue, Janjoter et al. discussed the interaction of Plasmodium genes with the mosquito genes that facilitate parasite invasion, and how the mosquito immune system defends itself from the invading parasite. 📕 Deciphering the molecular targets of Plasmodium and Anopheline interactions for malaria control 📖 Malaria, caused by Plasmodium and transmitted by female Anopheles mosquitoes, involves parasitic invasion of the mosquito midgut and salivary glands. These processes rely on interactions between parasite and mosquito proteins that aid immune evasion. Disrupting these proteins significantly reduces infection, suggesting their potential as targets for malaria control. This review highlights key proteins involved in transmission and gametogenesis, and their molecular interactions, to highlight effective malaria intervention strategies. Discover this brilliant Review, here ➡️ buff.ly/pXx0pJ3 ✍ Sangeeta Janjoter, Divya Kataria, Nisha Dahiya, Mahima Yadav, Hitesh Singh, Shilpi Garg, Neelam Sehrawat #malaria #plasmodium #mosquito #transmission #gametogenesis

📌 In this issue of The FEBS Journal, we highlight work by Wolverson et al., who developed a proximity labelling assay to investigate the CD9 interactome, a report by Graham and colleagues exploring antifreeze proteins in Clubiona spiders, and a study by Fitchner and co-authors, who created a fluorescence-based screening approach to investigate modulators of autophagy. We also feature promising studies by Coppola and co-authors and Watanabe et al., exploring the role of tgds in Catel–Manzke syndrome, and a new ‘Pod-TRECK’ mouse model to study chronic kidney disease, respectively. ☕ For a perfect weekend read, explore our Research Highlights for a glimpse into the brilliant work in Issue 8, featured by our Editorial Office. ➡️ buff.ly/0hKsR7s #proximitylabeling #antifreeze #autophagy #Catel–Manzkesyndrome #chronickidneydisease

🧠 We invite you to discover our latest Editor's Choice article and accompanying Commentary exploring the E3 ubiquitin ligase Praja and its critical role in neurodegeneration. 📕 E3 ligase Praja1 mediates ubiquitination and degradation of microtubule-associated protein tau 📖 The Praja family of RING-H2 type E3 ligases is composed of E3 ubiquitin–protein ligases Praja1 and Praja2, which promote the degradation of substrates through the ubiquitin–proteasome system. We show that Praja1, but not its paralogue Praja2, recognizes and ubiquitinates tau protein for proteasomal degradation. Efficient proteasomal degradation of aggregation-prone proteins, such as tau, is essential for neuroprotection. This newly identified function of Praja1 in tau degradation suggests its role in protein quality control, which may provide insights into the pathogenesis of tauopathies. Discover the article, here➡️ buff.ly/uCPcTnw ✍ Shiho Aoki, Wataru Onodera (小野寺 航), Akihiko Takashima, Kotaro Kawasaki, Kazuki Imadegawa, Hikaru Kurahashi, Mizuho Oishi, Toru ASAHI, Yoshiyuki Soeda Discover the related Commentary✍ Kazuhiko Watabe, here ➡️ buff.ly/1yXS184 #Praja #E3ligase #Tau #neurodegeneration #ubiquitination

@lukas_blaas and I wrote a commentary for the @FEBSJournal on the recent paper by Veliova et al. of the @OrianShirihai & @maroliufrj Labs. Fast & fuelious: the malate–aspartate shuttle in brown adipocyte lipid metabolism febs.onlinelibrary.wiley.com/doi/10.1111/fe…

🕷️ Have you ever wondered how some spiders survive the subzero temperatures? We're excited to highlight this compelling study on winter-active spiders from our latest Issue 8. 📕 Winter-active spiders (Clubiona) have a hyperactive antifreeze protein with a unique beta-solenoid fold 📖 Antifreeze proteins from winter-active spiders were purified using their affinity for ice. After LC–MSMS characterization, corresponding transcripts were identified. The antifreeze protein folds as a β-solenoid with a large flat ice-binding site on one surface and can bind to ice crystals and prevent their growth at −4 °C. Although some other antifreeze proteins also fold as β-solenoids, the spider protein is unique, indicating that it arose by convergent evolution. ✍ Laurie Graham, Stano Pekár, Ina M. Hainer, Peter L. Davies 🕸️ Discover more on 🕷️ , here ➡️ buff.ly/wxJfC2w #winteractivespiders #antifreeze #betasolenoids #crystal #clubiona

Prebiotic aqueous reactions catalyzed by native nickel without hydrogen #microbiology #OriginOfLife #geochemistry @FEBSJournal @FEBSnews doi.org/10.1111/febs.7…

💡 The clinical advancement of menin inhibitors represents a pivotal shift for the treatment of acute myeloid leukaemia (AML) characterized by specific genetic aberrations. 🧬 Our latest State-of-the-Art Review shares a comprehensive overview with a focus on KMT2A fusions in paediatric AML, and emphasizing their significance in the treatment with menin inhibitors. 📕 Current perspectives on KMT2A fusion proteins and menin inhibition in paediatric acute myeloid leukaemia 📖 Genetic rearrangements resulting in the expression of KMT2A fusion alleles can lead to dramatic transcriptional disturbances that contribute to the onset of acute leukaemias. Fortunately, menin inhibition has emerged as a promising new class of targeted therapy. These compounds work by blocking the protein–protein interaction between menin and KMT2A, which inhibits the transcription of downstream target genes and limits the progression of KMT2A-rearranged acute leukaemias. Discover the Review, here ➡️ febs.onlinelibrary.wiley.com/doi/10.1111/fe… ✍ Lydia Roets, Graeme Greenfield, Katrina Lappin #AML #menin #KMT2A #fusion #rearrangement

🚨 From molecular mechanisms to whole-organism models, Issue 8 is here! Our latest issue covers: 🧬 The State-of-the-Art Review on KMT2A fusion and menin inhibition in paediatric AML ☠️ A Viewpoint exploring chaperone-mediated autophagy 🌟 Research Highlights featuring excellent work published in The FEBS Journal 🧠 An Editor’s Choice article investigating the function of Praja1 in tau degradation 🚀 Several research articles spanning diverse life science topics including antifreeze proteins in winter-active spiders, a zebrafish model for Catel-Manzke syndrome, the CD9 interactome in epithelial cells, dietary effects on cardiac dysfunction, and more. Dive into this inspiring issue, here 👉 buff.ly/07kHuZL #modelorganisms #cardiacdysfunction #AML #autophagy #Tau

🗓️Save the date! The EMBO-EMBL Symposium, ‘Mechanobiology across the tree of life’, will take place this June, both virtually and in Heidelberg. 🎯This symposium will bring together researchers across all biological systems who will particularly focus on new technologies that empower studies of cell wall, cytoskeleton, and membrane biology, such as advanced imaging in in vitro and in vivo systems, as well as approaches combining molecular biology with computational and biophysical approaches. ⏰ Please note that the registration deadline for on-site attendance is 28th April, and for virtual attendance, it is 2nd June. The FEBS Journal has already registered, don't miss this excellent Symposium! For further details, please visit 👉buff.ly/0KUbdYs #EESMechanobiology #EMBLevents #FEBSPress

♀️ ♂️ We look forward to attending the EMBO-EMBL Symposium ‘Sex differences in health and disease’ in Heidelberg next week. 💬 Please come and meet The FEBS Journal Senior Editor, Hajrah Khawaja. We'd be delighted to connect and discuss great science with you! #EESSexDifferences #EMBLEvents #FEBSPress

🧩 We're delighted to present the State-of-the-Art Review from our latest issue discussing the role of molecular chaperones in translational control and how their dysfunction contributes to human disease. 📕 Molecular chaperones and proteostasis regulation during cytosolic translation 📖 Molecular chaperones work with the translation machinery to guide protein folding, prevent aggregation, and ensure proper protein localisation. This review highlights advances in understanding the role of chaperones in ribosome biogenesis, translation rate control, and fidelity. The findings expand the intricate connection between translation and chaperone machinery to maintain a functional proteome. Additionally, it stresses the need to apply insights from model organisms to understanding molecular mechanisms underlying human pathologies. Read the review, here ➡️ buff.ly/9BMWc25 ✍ Ulrike Topf #chaperone #translation #proteostasis #proteome

Excited to share our work in The FEBS Journal! We show how substrate specificity of lysine biosynthetic enzymes in Thermus thermophilus reveals the evolutionary link between lysine and arginine biosynthesis.febs.onlinelibrary.wiley.com/doi/10.1111/fe… @FEBSJournal