Characterization of the endogenous retrovirus ‐derived placenta‐specific soluble protein EnvV‐Fca from domestic cats
This study suggests that birds, bats, and rodents carrying EnvV2 may play significant roles as intermediate vectors in spreading or cross-transmitting viruses among species. Our findings provide valuable insights into the evolution of ERV in vertebrate hosts. (Source: FEBS Letters)
Source: FEBS Letters - April 12, 2024 Category: Biochemistry Authors: Didik Pramono,
Kenji Sugimoto,
Tohru Kimura,
Ariko Miyake,
Kazuo Nishigaki Tags: Research Article Source Type: research
Rejuvenating aged stem cells: therapeutic strategies to extend health and lifespan
Aging is associated with an impairment in stem cell function and several strategies for stem cell rejuvenation have been proposed: exercise, dietary restriction, reprogramming, senolytics, increasing autophagy, youthful blood factors exchange, and restoring cell polarity. Here, we review these strategies and their effects on rejuvenating stem cells in different tissues and underline when stem cell rejuvenation was able to improve health and lifespan. Aging is associated with a global decline in stem cell function. To date, several strategies have been proposed to rejuvenate aged stem cells: most of these result in function...
Source: FEBS Letters - April 12, 2024 Category: Biochemistry Authors: Francesca Matteini,
Sara Montserrat ‐Vazquez,
M. Carolina Florian Tags: In a Nutshell Source Type: research
The DMT1 isoform lacking the iron ‐response element regulates normal and malignant hematopoiesis via NOTCH pathway activation
In this report, we investigated the function of DMT1 nonIRE in normal and malignant hematopoiesis. Knockdown of Dmt1 nonIRE in mice showed that it has non-canonical functions in hematopoietic stem cell differentiation: its knockdown suppressed development along the myeloid and lymphoid lineages, while promoting the production of platelets. These phenotypic effects on the hematopoietic system induced by Dmt1 nonIRE knockdown were linked to suppression of Notch/Myc pathway activity. Conversely, our data indicate a non-canonical function for DMT1 nonIRE overexpression in boosting NOTCH pathway activity in T-cell leukemia home...
Source: FEBS Letters - April 10, 2024 Category: Biochemistry Authors: Judith Hounjet,
Linde Van Aerschot,
Kim De Keersmaecker,
Marc Vooijs,
Kim R. Kampen Tags: Research Letter Source Type: research
OTUD6A orchestrates complex modulation of TEAD4 ‐mediated transcriptional programs
In this study, we focused on transcriptional enhancer factor TEF-3 (TEAD4), exploring its regulation by the deubiquitinase OTU domain-containing protein 6A (OTUD6A). We identified OTUD6A as a TEAD4-interacting deubiquitinase, positively influencing TEAD-driven transcription without altering TEAD4 stability. Structural analyses revealed specific interaction domains: the N-terminal domain of OTUD6A and the YAP-binding domain of TEAD4. Functional assays demonstrated the positive impact of OTUD6A on the transcription of YAP –TEAD target genes. Despite no impact on TEAD4 nuclear localization, OTUD6A selectively modulated nucl...
Source: FEBS Letters - April 10, 2024 Category: Biochemistry Authors: Hyo Jin Kim,
Yunsik Choi,
Yuri Lee,
Mi Hwangbo,
Jongchan Kim Tags: Research Article Source Type: research
Hepatitis B virus ‐specific human stem cell memory T cells differentiate into cytotoxic T cells and eradicate HBV‐infected hepatocytes in mice
Here, we detected stem cell memory T cells (TSCMs) in chronic hepatitis B virus (HBV)-infected patients, using HBV core and polymerase peptide HLA tetramers. When these TSCMs were transferred into the human hepatocyte-transplanted, HBV-infected TK-NOG mouse, they differentiated into cytotoxic T lymphocytes, produced interferon gamma and interleukin-2, and developed histologically proven hepatitis. Furthermore, HBV DNA and human albumin in mouse serum declined and human hepatocytes were eliminated in the mouse model. Chronic infection with the hepatitis B virus (HBV) induces progressive hepatic impairment. Achieving complet...
Source: FEBS Letters - April 10, 2024 Category: Biochemistry Authors: Hiromi Abe ‐Chayama,
Takakazu Kawase,
Tatsuo Ichinohe,
Yuji Ishida,
Chise Tateno,
Makoto Hijikata,
Kazuaki Chayama Tags: Research Letter Source Type: research
Structural determinants for membrane binding of the EGFR juxtamembrane domain
The region containing residues I649 − L659 of the epidermal growth factor receptor (EGFR) juxtamembrane domain (JM) specifically interacts with PI(4,5)P2-or phosphatidylserine-containing membranes, suggesting that membrane binding may affect JM dimerization and, therefore, regulate EGFR kinase activation. Overactivation of the epidermal growth factor receptor (EGFR) is critical for the development of multiple cancers. Previous studies have shown that the cell membrane is a key regulator of EGFR kinase activity through its interaction with the EGFR juxtamembrane domain (JM). However, the lipid recognition specificity...
Source: FEBS Letters - April 9, 2024 Category: Biochemistry Authors: Ziwei Wu,
Ling Li,
Lina Zhu,
Runhan Wang,
Yingkui Dong,
Yaoyao Zhang,
Yujuan Wang,
Junfeng Wang,
Lei Zhu Tags: Research Letter Source Type: research
Front Cover
Cover illustration Membraneless organelles in posterior germ plasm of early Drosophila embryo incorporate protein clusters: Tudor (red), Aubergine (blue) and Pyruvate Kinase (green). This image is a composite of 164 optical sections. Please see the article by Wahiduzzamanet al. (Source: FEBS Letters)
Source: FEBS Letters - April 8, 2024 Category: Biochemistry Tags: Issue Information Source Type: research
Structural and functional insights of itaconyl ‐CoA hydratase from Pseudomonas aeruginosa highlight a novel N‐terminal hotdog fold
Here, we report the first crystal structure ofPaIch at 1.98 Å resolution. A unique N-terminal hotdog fold containing a short helical segment α3-, named an “eaten sausage”, slipped away from the conserved β-sheet scaffold, whereas central helices of other N- as well as C-terminal hotdog fold containing hydratases are properly wrapped up by their res pective β-sheet scaffold. Itaconyl-CoA hydratase inPseudomonas aeruginosa (PaIch) converts itaconyl-CoA to (S)-citramalyl-CoA upon addition of a water molecule, a part of an itaconate catabolic pathway in virulent organisms required for their survival in humans host c...
Source: FEBS Letters - April 5, 2024 Category: Biochemistry Authors: Atanu Pramanik,
Saumen Datta Tags: Research Article Source Type: research
Skraban ‐Deardorff intellectual disability syndrome‐associated mutations in WDR26 impair CTLH E3 complex assembly
The Skraban-Deardorff intellectual disability syndrome (SKDEAS) is associated with diverse mutations inWDR26, encoding a subunit required to assemble a giant oval-shaped supramolecular CTLH E3 ubiquitin ligase complex and substrate recruitment. Structural modeling of SKDEAS-associated mutations combined with functional assays revealed impaired CTLH E3 complex assembly and interactions, thus providing first mechanistic insights into SKDEAS pathology. Patients with Skraban-Deardorff syndrome (SKDEAS), a neurodevelopmental syndrome associated with a spectrum of developmental and intellectual delays and disabilities, harbor di...
Source: FEBS Letters - April 5, 2024 Category: Biochemistry Authors: Annette Gross,
Judith M üller,
Jakub Chrustowicz,
Alexander Strasser,
Karthik V. Gottemukkala,
Dawafuti Sherpa,
Brenda A. Schulman,
Peter J. Murray,
Arno F. Alpi Tags: Research Article Source Type: research
The scorpion toxin BeKm ‐1 blocks hERG cardiac potassium channels using an indispensable arginine residue
Using computational methods, we constructed a model of the cardiac ion channel hERG in complex with BeKm-1, a scorpion toxin. We identified the crucial role of the toxin residue Arg20 and validated it byin silico andin vitro mutagenesis. The BeKm-1R20K mutant showed dramatically reduced activity, suggesting the significance of Arg20 for channel binding. Our model aids future drug design attempts. BeKm-1 is a peptide toxin from scorpion venom that blocks the pore of the potassium channel hERG (Kv11.1) in the human heart. Although individual protein structures have been resolved, the structure of the complex between ...
Source: FEBS Letters - April 3, 2024 Category: Biochemistry Authors: Iana I. Zavarzina,
Alexey I. Kuzmenkov,
Nikita A. Dobrokhotov,
Ekaterina E. Maleeva,
Yuliya V. Korolkova,
Steve Peigneur,
Jan Tytgat,
Nikolay A. Krylov,
Alexander A. Vassilevski,
Anton O. Chugunov Tags: Research Article Source Type: research
Caspase ‐3 targets pro‐interleukin‐1β (IL‐1β) to restrict inflammation
The present study suggests pro-IL-1 β as a novel substrate of caspase-3. The activation of apoptotic signaling induces caspase-3 to cleave pro-IL-1β at the Asp26 site, and the generation of the Asp26 site restricts the inflammasome-mediated cleavage at the Asp117 site. Thus, caspase-3 prevents the release of mature IL-1β into the e xtracellular environment. The interleukin (IL)-1 family of cytokines plays a pivotal role in immune responses. Among the members of IL-1 family, IL-1 β is synthesized as an inactive precursor (pro-IL-1β) and becomes active upon cleavage, which is typically facilitated by inflammasomes throu...
Source: FEBS Letters - March 31, 2024 Category: Biochemistry Authors: Seon Sook Kim,
Su Ryeon Seo Tags: Research Letter Source Type: research
Cryo ‐EM structure of the Slo1 potassium channel with the auxiliary γ1 subunit suggests a mechanism for depolarization‐independent activation
γ subunits allow Slo potassium channels to open without an action potential. By cryo-EM structure determination, we show how γ1 binds the voltage-sensor domain (VSD) of Slo1. The kinked transmembrane helix and an extracellular hook of γ1 stabilize the VSD in its active conformation, while an intr acellular polybasic stretch locally decreases the resting potential. Mammalian Ca2+-dependent Slo K+ channels can stably associate with auxiliary γ subunits which fundamentally alter their behavior. By a so far unknown mechanism, the four γ subunits reduce the need for voltage-dependent activation and, thereby, allow Slo to o...
Source: FEBS Letters - March 30, 2024 Category: Biochemistry Authors: Milena Redhardt,
Stefan Raunser,
Tobias Raisch Tags: Research Letter Source Type: research
