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FEBS Letters

Michael M Lacy, Rui Ma, Neal G Ravindra, Julien Berro
During clathrin-mediated endocytosis (CME), a flat patch of membrane is invaginated and pinched off to release a vesicle into the cytoplasm. In yeast CME, over 60 proteins - including a dynamic actin meshwork - self-assemble to deform the plasma membrane. Several models have been proposed for how actin and other molecules produce the forces necessary to overcome the mechanical barriers of membrane tension and turgor pressure, but the precise mechanisms and a full picture of their interplay are still not clear...
July 14, 2018: FEBS Letters
Yongsoo Park, Je-Kyung Ryu
Vesicles in neurons and neuroendocrine cells store neurotransmitters and peptide hormones, which are released by vesicle fusion in response to Ca2+ -evoking stimuli. Synaptotagmin-1 (Syt1), a Ca2+ sensor, mediates ultrafast exocytosis in neurons and neuroendocrine cells. After vesicle docking, Syt1 has two main groups of binding partners: anionic phospholipids and the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) complex. The molecular mechanisms by which Syt1 triggers vesicle fusion remain controversial...
July 13, 2018: FEBS Letters
Xubo Lin, Hongyin Wang, Zhichao Lou, Meng Cao, Zuoheng Zhang, Ning Gu
In order to probe the roles of PIP2 in the interactions between MIM I-BAR and model membranes, we performed a series of 10μs-scale coarse-grained molecular dynamics simulations. Our results indicate that PIP2 plays predominant roles in the membrane binding of MIM I-BAR in a concentration-dependent manner and via electrostatic interactions. Besides, we find that the occurrence of the membrane curvature may induce the re-distribution of lipids in the membrane and result in the local enrichment of PIP2 at negatively curved membrane areas...
July 11, 2018: FEBS Letters
Suchita Pande, William Bizilj, Hwai-Chen Guo
Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by defects of the hydrolase glycosylasparaginase (GA). Previously, we showed that a Canadian AGU mutation disrupts an obligatory intra-molecular autoprocessing with the enzyme trapped as an inactive precursor. Here, we report biochemical and structural characterizations of a model enzyme corresponding to a Finnish AGU allele, the T234I variant. Unlike the Canadian counterpart, the Finnish variant is capable of a slow autoprocessing to generate detectible hydrolyzation activity of the natural substrate of GA...
July 11, 2018: FEBS Letters
Zeeshan Mutahir, Sophanit Mekasha, Jennifer S M Loose, Faiza Abbas, Gustav Vaaje-Kolstad, Vincent G H Eijsink, Zarah Forsberg
Lytic polysaccharide monooxygenases (LPMOs) contribute to enzymatic conversion of recalcitrant polysaccharides such as chitin and cellulose and may also play a role in bacterial infections. Some LPMOs are multi-modular, the implications of which remain only partly understood. We have studied the properties of a tetra-modular LPMO from the food poisoning bacterium Bacillus cereus (named BcLPMO10A). We show that BcLPMO10A, comprising an LPMO domain, two fibronectin-type III (FnIII)-like domains and a carbohydrate-binding module (CBM5), is a powerful chitin-active LPMO...
July 11, 2018: FEBS Letters
Mathias A Böhme, Andreas T Grasskamp, Alexander M Walter
Synaptic transmission relies on the rapid fusion of neurotransmitter-containing synaptic vesicles (SVs), which happens in response to action-potential (AP)-induced Ca2+ influx at active zones (AZs). A highly conserved molecular machinery cooperates at SV release sites to mediate SV-plasma membrane attachment and maturation, Ca2+ sensing, and membrane fusion. Despite this high degree of conservation, synapses -even within the same organism, organ or neuron- are highly diverse regarding the probability of APs to trigger SV fusion...
July 11, 2018: FEBS Letters
Xinxin Zhang, Philipp Köster, Kathrin Schlücking, Daria Balcerowicz, Kenji Hashimoto, Kazuyuki Kuchitsu, Kris Vissenberg, Jörg Kudla
Root hairs (RH) are tip growing polarized cells aiding the uptake of nutrients and water into plants. RH differentiation involves the interplay of various hormones and second messengers. Tightly regulated production of reactive oxygen species by the NADPH oxidase RBOHC crucially functions in RH differentiation and Ca2+ -dependent phosphorylation has been implemented in these processes. However, the kinases regulating RBOHC remained enigmatic. Here we identify CBL1-CIPK26 Ca2+ sensor-kinase complexes as modulators of RBOHC activity...
July 11, 2018: FEBS Letters
Toshiki Yabe-Wada, Shintaro Matsuba, Masaki Unno, Nobuyuki Onai
Sortilin is a multifunctional sorting receptor involved in cytokine production in immune cells. To understand the mechanism of Sortilin-mediated cytokine trafficking, we determined the 2.45-Å structure of the dimerized Sortilin ectodomain (sSortilin or the Vps10-domain) crystallized at acidic pH. Substantial conformational changes upon dimerization lead to the intermolecular hydrophobic interaction between the conserved E455 and F137. Analysis of the electrostatic surface and size-exclusion chromatography revealed that sSortilin dimerization occurrs due to an increase in hydrophobic interactions at the neutral dimer interface at acidic pH...
July 4, 2018: FEBS Letters
Matthew Johnson, Daniel P Mulvihill
The ability to regulate polarised cell growth is crucial to maintain the viability of cells. Growth is modulated to facilitate essential cell functions and respond to the external environment. Failure to do so can lead to numerous developmental and disease states, including cancer. We have undertaken a detailed analysis of the regulatory interplay between molecules involved in the regulation and maintenance of polarised cell growth within fission yeast. Internally controlled live cell imaging was used to examine interactions between 10 key polarity proteins...
July 4, 2018: FEBS Letters
Evangelia Lekka, Jonathan Hall
Non-coding RNAs (ncRNAs) are emerging as potent and multifunctional regulators in all biological processes. In parallel, a rapidly-growing number of studies has unravelled associations between aberrant non-coding RNA expression and human diseases. These associations have been extensively reviewed, often with the focus on a particular miRNA (family) or a selected disease/pathology. In this Mini-Review, we highlight a selection of studies in order to demonstrate the widescale involvement of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the pathophysiology of three types of diseases: cancer, cardiovascular and neurological disorders...
July 4, 2018: FEBS Letters
Cecilia Lanny Winata, Vladimir Korzh
Since their discovery, the study of maternal mRNAs has led to the identification of mechanisms underlying their spatiotemporal regulation within the context of oogenesis and early embryogenesis. Following synthesis in the oocyte, maternal mRNAs are translationally silenced and sequestered into storage in cytoplasmic granules. At the same time, their unique distribution patterns throughout the oocyte and embryo are tightly controlled and connected to their functions in downstream embryonic processes. At certain points in oogenesis and early embryogenesis, maternal mRNAs are translationally activated to perform their functions in a timely manner...
July 4, 2018: FEBS Letters
Aldo Meizoso-Huesca, Sócrates Villegas-Comonfort, M Teresa Romero-Ávila, J Adolfo García-Sáinz
The crosstalk between the free fatty acid receptor FFA4 and the lysophosphatidic acid receptor LPA1 seems to be of pathophysiological importance. We explored this crosstalk employing co-expression of fluorescent protein-tagged receptors. FFA4 activation induces functional desensitization of LPA1 receptors and phosphorylation of both receptors. LPA1 activation induces phosphorylation of LPA1 , but not of FFA4, and induces internalization of both receptors into heterogeneous types of vesicles. Docosahexaenoic acid (DHA) induces internalization of FFA4 but not of LPA1 ...
July 3, 2018: FEBS Letters
Satoshi Funaya, Masatoshi Ooga, Masataka G Suzuki, Fugaku Aoki
The chromatin structure in one-cell-stage mouse embryos is extremely loose and becomes tighter at the two-cell stage. Because linker histones are involved in higher-order chromatin structure, we examined the involvement of the linker histone variant H1foo in the change of chromatin looseness between the one- and two-cell stages. H1foo knockdown causes the chromatin structure to be tighter in the pronucleus and increases deposition of the histone H3 variant H3.1/3.2 in the peripheral region of the pronucleus in one-cell-stage embryos...
July 2, 2018: FEBS Letters
Virginia Garcia-Martinez, Yolanda Gimenez-Molina, José Villanueva, Frederic D Darios, Bazbek Davletov, Luis M Gutiérrez
Membrane fusion is a key event in exocytosis of neurotransmitters and hormones stored in intracellular vesicles. In this process, SNARE proteins are essential components of the exocytotic molecular machinery, while lipids have been seen traditionally as structural elements. However, the so-called signalling lipids, such as sphingosine and arachidonic acid, interact with SNAREs and directly modulate the frequency and mode of fusion events. Interestingly, recent work has proved that the sphingosine analogue FTY-720, used in the treatment of multiple sclerosis, mimics the effects of signalling lipids...
July 1, 2018: FEBS Letters
Hanako Ishida, Umeharu Ohto, Takuma Shibata, Kensuke Miyake, Toshiyuki Shimizu
Single-stranded DNA containing unmethylated CpG motifs derived from microorganisms are recognized by Toll-like receptor (TLR) 9 and activate an innate immune response. TLR9 has two DNA-binding sites for CpG DNA and DNA containing cytosine at the second position from the 5'-end; both are required for efficient TLR9 activation in most vertebrate species. However, mouse TLR9 can be dimerized by CpG DNA only, although the underlying mechanism remains elusive. Here, we report the crystal structure of mouse TLR9 complexed with both DNAs...
July 1, 2018: FEBS Letters
Ieva Bagdonaite, Sergey Y Vakhrushev, Hiren J Joshi, Hans H Wandall
It has long been known that surface proteins of most enveloped viruses are covered with glycans. It has furthermore been demonstrated that glycosylation is essential for propagation and immune evasion for many viruses. The recent development of high resolution mass spectrometry techniques has enabled identification not only of the precise structures but also the positions of such post-translational modifications on viruses, revealing substantial differences in extent of glycosylation and glycan maturation for different classes of viruses...
July 1, 2018: FEBS Letters
Anand S Sandholu, Madhura Mohole, William L Duax, Hirekodathakallu V Thulasiram, Durba Sengupta, Kiran Kulkarni
Iridoid synthases belong to the family of short-chain dehydrogenase/reductase involved in the biosynthesis of iridoids. Despite having high sequence and structural homology with progesterone 5β-reductase, these enzymes exhibit differential substrate specificities. Previously, two loops, L1 and L2 at substrate binding pocket, were suggested to be involved in generating substrate specificity. However, the structural basis of specificity determinants were elusive. Here, combining sequence and structural analysis, site-directed mutagenesis and molecular dynamics simulations, we have shown that iridoid synthase contains two channels for substrate entry whose geometries are altered by L1-L2 dynamics, primarily orchestrated by interactions of residues Glu161 & Gly162 of L1 and Asn358 of L2...
June 26, 2018: FEBS Letters
Theresia E B Stradal, Mario Schelhaas
The actin cytoskeleton and Rho GTPase signaling to actin assembly are prime targets of bacterial and viral pathogens, simply because actin is involved in all motile and membrane remodeling processes, such as phagocytosis, macropinocytosis, endocytosis, exocytosis, vesicular trafficking and membrane fusion events, motility, and last, but not least, autophagy. This article aims at providing an overview of the most prominent pathogen-induced or -hijacked actin structures, and an outlook on how future research might uncover additional, equally sophisticated interactions...
June 23, 2018: FEBS Letters
Mathias Cobbaut, Rita Derua, Peter J Parker, Etienne Waelkens, Veerle Janssens, Johan Van Lint
The protein kinase D (PKD) family is regulated through multi-site phosphorylation, including autophosphorylation. For example, PKD displays in vivo autophosphorylation on Ser-742 (and Ser-738 in vitro) in the activation loop and Ser-910 in the C-tail (hPKD1 numbering). In this paper, we describe the surprising observation that PKD also displays in vitro autocatalytic activity towards a Tyr residue in the P+1 loop of the activation segment. We define the molecular determinants for this unusual activity and identify a Cys residue (C705 in PKD1) in the catalytic loop as of utmost importance...
June 22, 2018: FEBS Letters
Yujuan Wang, Jing Yang, Jiarong Wang, Lei Zhu, Junfeng Wang
PB1F2 is a proapoptotic protein encoded by an alternative reading frame in the influenza A virus. Its accumulation accelerates mitochondrial fragmentation by decreasing the mitochondrial membrane potential following translocation into the mitochondrial inner membrane space, but the mechanistic underpinnings remain unclear. Herein, the PB1F2 from HK97 was expressed and purified in soluble form. The interaction between PB1F2 and the mitochondrial membrane were investigated using three membrane mimics, liposomes, bicelles and nanodiscs...
June 22, 2018: FEBS Letters
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