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Membrane fusion

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https://www.readbyqxmd.com/read/29453458/il-2-inducible-kinase-itk-is-critical-for-hiv-1-infection-of-jurkat-t-cells
#1
Anika Hain, Melanie Krämer, René M Linka, Saeideh Nakhaei-Rad, Mohammad Reza Ahmadian, Dieter Häussinger, Arndt Borkhardt, Carsten Münk
Successful replication of Human immunodeficiency virus (HIV)-1 depends on the expression of various cellular host factors, such as the interleukin-2 inducible T-cell kinase (ITK), a member of the protein family of TEC-tyrosine kinases. ITK is selectively expressed in T-cells and coordinates signaling pathways downstream of the T-cell receptor and chemokine receptors, including PLC-1 activation, Ca 2+ -release, transcription factor mobilization, and actin rearrangements. The exact role of ITK during HIV-1 infection is still unknown...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29452143/unusual-self-assembly-of-the-recombinant-chlamydia-trachomatis-major-outer-membrane-protein-momp-based-fusion-antigen-cth522-into-protein-nanoparticles
#2
Fabrice Rose, Kasper Karlsen, Pernille Rønde Jensen, Rasmus Uffe Jakobsen, Grith Krøyer Wood, Kasper Dyrberg Rand, Helene Godiksen, Peter Andersen, Frank Follmann, Camilla Foged
Sexually transmitted Chlamydia trachomatis (Ct) infects more than 100 million people annually, and untreated chlamydia infections can cause severe complications. Therefore, there is an urgent need for a chlamydia vaccine. The Ct major outer membrane protein (MOMP) is highly immunogenic but is a challenging vaccine candidate by being an integral membrane protein, and the immunogenicity depends on a correctly folded structure. We investigated the biophysical properties of the recombinant MOMP-based fusion antigen CTH522, which is tested in early human clinical trials...
February 13, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29451720/detection-of-membrane-protein-protein-interaction-in-planta-based-on-dual-intein-coupled-tripartite-split-gfp-association
#3
Tzu-Yin Liu, Wen-Chun Chou, Wei-Yuan Chen, Ching-Yi Chu, Chen-Yi Dai, Pei-Yu Wu
Despite a great interest of identification of protein-protein interactions (PPIs) in biological systems, only few attempts have been made for a large-scale PPI screen in planta. Unlike biochemical assays, bimolecular fluorescence complementation (BiFC) allows visualization of the transient and weak PPIs in vivo at the subcellular resolution. However, when the non-fluorescent fragments are highly expressed, the spontaneous and irreversible self-assembly of the split halves can easily generate false positives...
February 16, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29449316/snareing-an-arp-requires-a-lir
#4
Sharon A Tooze
The fusion of autophagosomes with lysosomes is an obligatory step in the self-eating process of autophagy. In this issue, Kumar et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201708039) identify a protein complex, the autophagosome recognition particle (ARP), that chaperones a key SNARE, syntaxin 17, to the autophagosome membrane. Intriguingly, this protein complex coordinates both delivery and membrane insertion as a prelude to fusion.
February 15, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29448966/exosomes-taken-up-by-neurons-hijack-the-endosomal-pathway-to-spread-to-interconnected-neurons
#5
Juan Carlos Polanco, Chuanzhou Li, Nela Durisic, Robert Sullivan, Jürgen Götz
In Alzheimer disease and related disorders, the microtubule-associated protein tau aggregates and forms cytoplasmic lesions that impair neuronal physiology at many levels. In addition to affecting the host neuron, tau aggregates also spread to neighboring, recipient cells where the misfolded tau aggregates, in a manner similar to prions, actively corrupt the proper folding of soluble tau, and thereby impair cellular functions. One vehicle for the transmission of tau aggregates are secretory nanovesicles known as exosomes...
February 15, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29447976/identification-of-a-novel-host-protein-sinal10-interacting-with-gp64-and-its-role-in-bombyx-mori-nucleopolyhedrovirus-infection
#6
Min Feng, Xiangshuo Kong, Jianjia Zhang, Weifan Xu, Xiaofeng Wu
Bombyx mori nucleopolyhedrovirus (BmNPV) is the most important pathogen of Bombyx mori, silkworm and causes severe losses in the silk industry. During the virus infectious cycle, budded virus (BVs) and occlusion-derived virus (ODVs) particles, which have identical genetic content but different phenotypes, are produced. The envelope glycoprotein GP64, specific in BVs, is involved in host cell receptor binding and is sufficient to mediate membrane fusion during the viral entry. However, the host cell factors, interacting with GP64 to mediate BVs infection, are still unknown...
February 12, 2018: Virus Research
https://www.readbyqxmd.com/read/29447917/insertion-of-dengue-e-into-lipid-bilayers-studied-by-neutron-reflectivity-and-molecular-dynamics-simulations
#7
Juan M Vanegas, Frank Heinrich, David M Rogers, Bryan D Carson, Sadie La Bauve, Briana C Vernon, Bulent Akgun, Sushil Satija, Aihua Zheng, Margaret Kielian, Susan B Rempe, Michael S Kent
The envelope (E) protein of Dengue virus rearranges to a trimeric hairpin to mediate fusion of the viral and target membranes, which is essential for infectivity. Insertion of E into the target membrane serves to anchor E and possibly also to disrupt local order within the membrane. Both aspects are likely to be affected by the depth of insertion, orientation of the trimer with respect to the membrane normal, and the interactions that form between trimer and membrane. In the present work, we resolved the depth of insertion, the tilt angle, and the fundamental interactions for the soluble portion of Dengue E trimers (sE) associated with planar lipid bilayer membranes of various combinations of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol (POPG), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), and cholesterol (CHOL) by neutron reflectivity (NR) and by molecular dynamics (MD) simulations...
February 12, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29446751/molecular-mechanism-to-target-the-endosomal-mon1-ccz1-gef-complex-to-the-pre-autophagosomal-structure
#8
Jieqiong Gao, Lars Langemeyer, Daniel Kuemmel, Fulvio Reggiori, Christian Ungermann
During autophagy, a newly formed double membrane surrounds its cargo to generate the so-called autophagosome, which then fuses with a lysosome after closure. Previous work implicated that endosomal Rab7/Ypt7 associates to autophagosomes prior to their fusion with lysosomes. Here, we unravel how the Mon1-Ccz1 guanosine exchange factor (GEF) acting upstream of Ypt7 is specifically recruited to the pre-autophagosomal structure under starvation conditions. We find that Mon1-Ccz1 directly binds to Atg8, the yeast homolog of the members of the mammalian LC3 protein family...
February 15, 2018: ELife
https://www.readbyqxmd.com/read/29445128/the-brace-helices-of-mlkl-mediate-interdomain-communication-and-oligomerisation-to-regulate-cell-death-by-necroptosis
#9
Katherine A Davies, Maria C Tanzer, Michael D W Griffin, Yee Foong Mok, Samuel N Young, Rui Qin, Emma J Petrie, Peter E Czabotar, John Silke, James M Murphy
The programmed cell death pathway, necroptosis, relies on the pseudokinase, Mixed Lineage Kinase domain-Like (MLKL), for cellular execution downstream of death receptor or Toll-like receptor ligation. Receptor-interacting protein kinase-3 (RIPK3)-mediated phosphorylation of MLKL's pseudokinase domain leads to MLKL switching from an inert to activated state, where exposure of the N-terminal four-helix bundle (4HB) 'executioner' domain leads to cell death. The precise molecular details of MLKL activation, including the stoichiometry of oligomer assemblies, mechanisms of membrane translocation and permeabilisation, remain a matter of debate...
February 14, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29445117/transitional-correlation-between-inner-membrane-potential-and-atp-levels-of-neuronal-mitochondria
#10
R Suzuki, K Hotta, K Oka
The importance of highly active mitochondria and their contribution to neuronal function has been of recent interest. In most cases, however, mitochondrial activity is estimated using measurements of mitochondrial inner membrane potential (IMP mito ), and little is known about the dynamics of native mitochondrial ATP (ATP mito ). This study conducted simultaneous imaging of IMP mito and ATP mito in neurons to explore their behaviour and their correlation during physiological mitochondrial/neuronal activity...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29444959/the-synaptotagmin-c2b-domain-calcium-binding-loops-modulate-the-rate-of-fusion-pore-expansion
#11
Mounir Bendahmane, Kevin P Bohannon, Mazdak M Bradberry, Tejeshwar C Rao, Michael W Schmidtke, Prabhodh S Abbineni, Nara L Chon, Sherleen Tran, Hai Lin, Edwin R Chapman, Jefferson D Knight, Arun Anantharam
In chromaffin cells, the kinetics of fusion pore expansion vary depending on which synaptotagmin isoform (Syt-1 or Syt-7) drives release. Our recent studies have shown that fusion pores of granules harboring Syt-1 expand more rapidly than those harboring Syt-7. Here, we sought to define the structural specificity of synaptotagmin action at the fusion pore by manipulating the Ca 2+ -binding C2B module. We generated a chimeric Syt-1 in which its C2B Ca 2+ -binding loops had been exchanged for those of Syt-7. Fusion pores of granules harboring a Syt-1 C2B chimera with all three Ca 2+ -binding loops of Syt-7 (Syt-1:7C2B 123 ) exhibited slower rates of fusion pore expansion and neuropeptide cargo release relative to WT Syt-1...
February 14, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29444306/mpamt1-2-from-marchantia-polymorpha-is-a-high-affinity-plasma-membrane-ammonium-transporter
#12
Hanqing Guo, Nu Wang, Tami R McDonald, Anke Reinders, John M Ward
Plant ammonium transporters in the AMT/MEP/Rh superfamily have only been previously characterized in flowering plants (angiosperms). Plant AMT1s are electrogenic, while plant AMT2s are electroneutral and MEP and Rh transporters in other organisms are electroneutral. We analyzed the transport function of MpAMT1;2 from the basal land plant Marchantia polymorpha, a liverwort. MpAMT1;2 was shown to localize to the plasma membrane in Marchantia gametophyte thallus by stable transformation using a C-terminal citrine fusion...
February 12, 2018: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29443945/charged-n-terminus-of-influenza-fusion-peptide-facilitates-membrane-fusion
#13
Remigiusz Worch, Anita Dudek, Joanna Krupa, Anna Szymaniec, Piotr Setny
Cleavage of hemagglutinin precursor (HA0) by cellular proteases results in the formation of two subunits, HA1 and HA2. The N-terminal fragment of HA2, named a fusion peptide (HAfp), possess a charged, amine N-terminus. It has been shown that the N-terminus of HAfp stabilizes the structure of a helical hairpin observed for a 23-amino acid long peptide (HAfp1-23), whose larger activity than HAfp1-20 has been demonstrated recently. In this paper, we analyze the effect of N-terminal charge on peptide-mediated fusion efficiency and conformation changes at the membrane interface by comparison with the corresponding N -acetylated peptides of 20- and 23-amino acid lengths...
February 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29442512/discovery-of-hydrocarbon-stapled-short-%C3%AE-helical-peptides-as-promising-middle-east-respiratory-syndrome-coronavirus-mers-cov-fusion-inhibitors
#14
Chao Wang, Shuai Xia, Peiyu Zhang, Tianhong Zhang, Weicong Wang, Yangli Tian, Guangpeng Meng, Shibo Jiang, Keliang Liu
The hexameric α-helical coiled-coil formed between the C-terminal and N-terminal heptad repeat (CHR and NHR) regions of class I viral fusion proteins plays an important role in mediating the fusion of the viral and cellular membranes and provides a clear starting point for molecular mimicry that drives viral fusion inhibitor design. Unfortunately, such peptide mimicry of the short α-helical region in the CHR of Middle East respiratory syndrome coronavirus (MERS-CoV) spike protein has been thwarted by the loss of the peptide's native α-helical conformation when taken out of the parent protein structure...
February 14, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29439644/potential-hiv-1-fusion-inhibitors-mimicking-gp41-specific-broadly-neutralizing-antibody-10e8-in-silico-discovery-and-prediction-of-antiviral-potency
#15
Alexander M Andrianov, Ivan A Kashyn, Alexander V Tuzikov
An integrated computational approach to in silico drug design was used to identify novel HIV-1 fusion inhibitor scaffolds mimicking broadly neutralizing antibody (bNab) 10E8 targeting the membrane proximal external region (MPER) of the HIV-1 gp41 protein. This computer-based approach included (i) generation of pharmacophore models representing 3D-arrangements of chemical functionalities that make bNAb 10E8 active towards the gp41 MPER segment, (ii) shape and pharmacophore-based identification of the 10E8-mimetic candidates by a web-oriented virtual screening platform pepMMsMIMIC, (iii) high-throughput docking of the identified compounds with the gp41 MPER peptide, and (iv) molecular dynamics simulations of the docked structures followed by binding free energy calculations...
January 15, 2018: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/29438347/mitochondrial-dynamics-in-basal-and-stressful-conditions
#16
REVIEW
Naima Zemirli, Etienne Morel, Diana Molino
The historical role of mitochondria resides in converting the energy released during the oxidation of macromolecules (carbohydrates, lipids and proteins) into adenosine tri-phosphate, a major form of chemically stored energy which sustains cell growth and homeostasis. Beyond this role in bioenergetics regulation, mitochondria play a role in several other cellular processes including lipid metabolism, cellular calcium homeostasis, autophagy and immune responses. Furthermore, mitochondria are highly dynamic organelles: as all other cellular endomembranes, they are continuously moving along cytoskeleton, and, most importantly, they constantly interact one with each other by membrane tethering, fusion and fission...
February 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29436730/ultrastructural-description-of-the-spermatogenesis-and-spermatozoa-in-phaenocora-unipunctata-platyhelminthes-neotyphloplanida
#17
Rodrigo Ponce de León, Odile Volonterio
Ultrastructural studies of spermiogenesis and sperm morphology have found many characters that are likely to provide clues to the phylogeny of the Platyhelminthes. However, the lack of information on many free-living groups has been a limiting factor. There is a single description of the spermatogenesis and spermatozoa in a Phaenocora species, namely P. anomalocoela, therefore a similar analysis was made in Phaenocora unipunctata to compare the intrageneric variation of sperm ultrastructure and spermatogenesis in the Neotyphloplanida...
February 13, 2018: Journal of Morphology
https://www.readbyqxmd.com/read/29436366/spermiogenesis-and-spermatozoon-ultrastructure-in-basal-polyopisthocotylean-monogeneans-hexabothriidae-and-chimaericolidae-and-their-significance-for-the-phylogeny-of-the-monogenea
#18
Jean-Lou Justine, Larisa G Poddubnaya
Sperm ultrastructure provides morphological characters useful for understanding phylogeny; no study was available for two basal branches of the Polyopisthocotylea, the Chimaericolidea and Diclybothriidea. We describe here spermiogenesis and sperm in Chimaericola leptogaster (Chimaericolidae) and Rajonchocotyle emarginata (Hexabothriidae), and sperm in Callorhynchocotyle callorhynchi (Hexabothriidae). Spermiogenesis in C. leptogaster and R. emarginata shows the usual pattern of most Polyopisthocotylea with typical zones of differentiation and proximo-distal fusion of the flagella...
2018: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/29433439/legionella-effector-ankx-interacts-with-host-nuclear-protein-plekhn1
#19
Xiaobo Yu, Rebecca R Noll, Barbara P Romero Dueñas, Samual C Allgood, Kristi Barker, Jeffrey L Caplan, Matthias P Machner, Joshua LaBaer, Ji Qiu, M Ramona Neunuebel
BACKGROUND: The intracellular bacterial pathogen Legionella pneumophila proliferates in human alveolar macrophages, resulting in a severe pneumonia termed Legionnaires' disease. Throughout the course of infection, L. pneumophila remains enclosed in a specialized membrane compartment that evades fusion with lysosomes. The pathogen delivers over 300 effector proteins into the host cell, altering host pathways in a manner that sets the stage for efficient pathogen replication. The L. pneumophila effector protein AnkX targets host Rab GTPases and functions in preventing fusion of the Legionella-containing vacuole with lysosomes...
January 5, 2018: BMC Microbiology
https://www.readbyqxmd.com/read/29432843/the-neuronal-protection-of-a-zinc-binding-protein-isolated-from-oyster
#20
Wei-Hsuan Hsu, Yu-Chun Lin, Bo-Rui Chen, She-Ching Wu, Bao-Hong Lee
Mitochondrial function is applied as oxidative stress and neuronal damage index. In this study, d-galactose was used to induce free radicals production and neuronal damage in HN-h cells, and the effect of novel 43 kDa protein isolated from oyster on anti-mitochondrial dysfunction and zinc-binding ability were evaluated. Crystal violet stain results indicated zinc-binding protein of oyster (ZPO) attenuated neuronal cell death induced by 100 mM of d-galactose on HN-h cells in a dose-dependent manner. ZPO alleviated mitochondrial inactivation, mitochondrial membrane potential decreasing, oxidative stress, and fusion/fission state in non-cytotoxic concentration of d-galactose (50 mM)-treated HN-h cells...
February 9, 2018: Food and Chemical Toxicology
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