A two ‐step mechanism for the binding of the HIV‐1 MPER epitope by the 10E8 antibody onto biosensor‐supported lipid bilayers
MPER-targeting antibodies display nearly pan-neutralizing activity against HIV. Elucidating the mechanisms of epitope recognition by these antibodies is paramount for developing preventive vaccines and antibody-based treatments. Here, we report that binding of 10E8 to the MPER helix epitope presented in the membrane microenvironment occurs in two steps: (i) engagement with the solvent-exposed MPER portion; and (ii) accommodation of the membrane surface. HIV-1 antibodies targeting the carboxy-terminal area of the membrane-proximal external region (ctMPER) are close to exerting viral pan-neutralization. Here, we reconstitute...
Source: FEBS Letters - February 10, 2024 Category: Biochemistry Authors: Miguel Garc ía‐Porras,
Johana Torralba,
Sara Insausti,
Javier Valle,
David Andreu,
Beatriz Apellániz,
José L. Nieva Tags: Research Article Source Type: research
Osmotic stress induces the formation of migrasome ‐like vesicles
In this study, we report the formation of migrasome-like vesicles enriched in tetraspanin 4 and containing cytoplasmic components in response to hypoosmotic stress. When migrating cells were subjected to hypoosmotic stress, vesicles with a size distribution of 0.5 to 2 μm formed on the retraction fibers, and vanished in a few minutes. The vesicles are rich in cholesterol, and their number was reduced when cells were pretreated with lipoprotein-deficient serum. The formation of migrasome-like vesicles upon hypoosmotic stress may provide biophysical cues regardi ng the cellular response to this external stimulus in cells...
Source: FEBS Letters - February 10, 2024 Category: Biochemistry Authors: Koki Yoshikawa,
Shogo Saito,
Tetsuya Kadonosono,
Masayoshi Tanaka,
Mina Okochi Tags: Research Letter Source Type: research
The lipid ‐binding D4 domain of perfringolysin O facilitates the active loading of exogenous cargo into extracellular vesicles
This study investigates the role of domain 4 (D4), a cholesterol-binding domain as a viable candidate for extracellular vesicle (EV) protein loading and cargo delivery. D4 recognizes cholesterol in the EV membrane and recruits proteins of interest into EVs. Our experiments using split-nano luciferase technology enhanced by fusogenic vesicular stomatitis virus glycoprotein also demonstrate the capability of D4-engineered EVs for intracellular protein delivery. Whereas extracellular vesicles (EVs) have been engineered for cargo loading, innovative strategies for it can still be developed. Here, we describe domain 4 (D4), a c...
Source: FEBS Letters - February 10, 2024 Category: Biochemistry Authors: Abayomi Emmanuel Opadele,
Soichiro Nishioka,
Ping ‐Hsiu Wu,
Quynh‐Thu Le,
Hiroki Shirato,
Jin‐Min Nam,
Yasuhito Onodera Tags: Research Letter Source Type: research
A two ‐step mechanism for the binding of the HIV‐1 MPER epitope by the 10E8 antibody onto biosensor‐supported lipid bilayers
MPER-targeting antibodies display nearly pan-neutralizing activity against HIV. Elucidating the mechanisms of epitope recognition by these antibodies is paramount for developing preventive vaccines and antibody-based treatments. Here, we report that binding of 10E8 to the MPER helix epitope presented in the membrane microenvironment occurs in two steps: (i) engagement with the solvent-exposed MPER portion; and (ii) accommodation of the membrane surface. HIV-1 antibodies targeting the carboxy-terminal area of the membrane-proximal external region (ctMPER) are close to exerting viral pan-neutralization. Here, we reconstitute...
Source: FEBS Letters - February 9, 2024 Category: Biochemistry Authors: Miguel Garc ía‐Porras,
Johana Torralba,
Sara Insausti,
Javier Valle,
David Andreu,
Beatriz Apellániz,
José L. Nieva Tags: Research Article Source Type: research
Lipid droplets provide metabolic flexibility for cancer progression
The accumulation of lipid droplets (LDs) is increasingly recognized as a new hallmark of cancer. In this review, we unravel the role of LDs and three major classes of LD-resident proteins —perilipins, lipases, and acyl-CoA synthetases—in providing metabolic flexibility to cancer cells which enable them to proliferate, invade, metastasize, defy hypoxia, and upsurge their stemness capacity. A hallmark of cancer cells is their remarkable ability to efficiently adapt to favorable and hostile environments. Due to a unique metabolic flexibility, tumor cells can grow even in the absence of extracellular nutrients or in stress...
Source: FEBS Letters - February 8, 2024 Category: Biochemistry Authors: R émi Safi,
Pablo Menéndez,
Albert Pol Tags: Review Source Type: research
MATR3 pathogenic variants differentially impair its cryptic splicing repression function
MATR3 is a splicing regulator implicated in neurodegenerative and neurodevelopmental diseases, but its role in cryptic splicing repression within functional genes is unclear. Here, we show that MATR3 loss leads to cryptic exon inclusion in many functional genes. We also show that two disease-associated variants differentially affect MATR3 properties, solubility, and RNA binding, thereby impacting its cryptic splicing repression function. Matrin-3 (MATR3) is an RNA-binding protein implicated in neurodegenerative and neurodevelopmental diseases. However, little is known regarding the role of MATR3 in cryptic splicing within ...
Source: FEBS Letters - February 7, 2024 Category: Biochemistry Authors: Mashiat Khan,
Xiao Xiao Lily Chen,
Michelle Dias,
Jhune Rizsan Santos,
Sukhleen Kour,
Justin You,
Rebekah van Bruggen,
Mohieldin M. M. Youssef,
Ying ‐Wooi Wan,
Zhandong Liu,
Jill A. Rosenfeld,
Qiumin Tan,
Udai Bhan Pandey,
Hari Krishna Yala Tags: Research Article Source Type: research
Remodelling of mitochondrial function by import of specific lipids at multiple membrane ‐contact sites
Metabolic homeostasis depends on the functional remodeling of organelles. During starvation, this is especially evident for mitochondria. In this perspective, we outline a possible mechanism by which lipid transport at membrane contact sites might control the adaptation of mitochondrial activities. We conclude with the notion that mitochondria interact with a whole network of organelles to achieve this important physiological task. Organelles form physical and functional contact between each other to exchange information, metabolic intermediates, and signaling molecules. Tethering factors and contact site complexes bring p...
Source: FEBS Letters - February 5, 2024 Category: Biochemistry Authors: Aksel J. Saukko ‐Pavola,
Robin W. Klemm Tags: Perspective Source Type: research
The prefoldin ‐like protein AtURI exhibits characteristics of intrinsically disordered proteins
The prefoldin-like protein AtURI has a large, disordered region (colored red) at the C-terminus of the structured prefoldin domain (colored blue) that confers AtURI promiscuity for protein –protein interactions and instability to allow tight control of AtURI levels. The prefoldin-like protein UNCONVENTIONAL PREFOLDIN RPB5 INTERACTOR (URI) participates in diverse cellular functions, including protein homeostasis, transcription, translation, and signal transduction. Thus, URI is a highly versatile protein, although the molecular basis of this versatility remains unknown. In this work, we show thatArabidopsis thaliana (Arab...
Source: FEBS Letters - February 2, 2024 Category: Biochemistry Authors: Yaiza G ómez‐Mínguez,
Alberto Palacios‐Abella,
Cecilia Costigliolo‐Rojas,
Mariana Barber,
Laura Hernández‐Villa,
Cristina Úrbez,
David Alabadí Tags: Research Article Source Type: research
Mdm2 ‐mediated ubiquitination of PKCβII is responsible for insulin‐induced heterologous desensitization of dopamine D3 receptor
In response to insulin stimulation, the E3 ligase enzyme Mdm2 exits the nucleus and interacts with PKC βII, facilitating the ubiquitination of PKCβII. Subsequently, the ubiquitinated PKCβII translocates to the cell membrane and associates with D3R, resulting in the inhibition of D3R cAMP signaling and linking it to clathrin-mediated endocytosis and degradation. The insulin and dopaminergic systems in the brain are associated with schizophrenia and Parkinson's disease with respect to etiology and treatment. The present study investigated the crosstalk between the insulin receptor (IR) and dopamine receptor and found that...
Source: FEBS Letters - February 2, 2024 Category: Biochemistry Authors: Xingyue Zeng,
ChengYan Wu,
Yongkai Cao,
Huijun Li,
Xiaohan Zhang Tags: Research Article Source Type: research
Mitochondrial dysfunction in NPC1 ‐deficiency is not rescued by drugs targeting the glucosylceramidase GBA2 and the cholesterol‐binding proteins TSPO and StARD1
We examined two potential protein targets—translocator protein (TSPO) and steroidogenic acute regulatory protein D1 (StARD1)—which are implicated in cholesterol transport to mitochondria, in addition to glucocerbrosidase 2 (GBA2), the target of miglustat, which is currently the only approved treatment for NPCD. However, inhibiting these proteins did not correct the mitochondrial defect in NPC1-deficient cells. (Source: FEBS Letters)
Source: FEBS Letters - February 2, 2024 Category: Biochemistry Authors: Simon Wheeler,
Meenakshi Bhardwaj,
Victor Kenyon,
Maria J. Ferraz,
Johannes M. F. G. Aerts,
Dan J. Sillence Tags: Communication Source Type: research
Front Cover
Cover illustration The cover image refers to the article by Buechel and Pinkett ‘Activity of the pleiotropic drug resistance transcription factors Pdr1p and Pdr3p is modulated by binding site fl anking sequences’ (Source: FEBS Letters)
Source: FEBS Letters - January 29, 2024 Category: Biochemistry Tags: Issue Information Source Type: research
