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membrane protein folding

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https://www.readbyqxmd.com/read/28806784/structural-analysis-of-p-falciparum-kahrp-and-pfemp1-complexes-with-host-erythrocyte-spectrin-suggests-a-model-for-cytoadherent-knob-protrusions
#1
Erin E Cutts, Niklas Laasch, Dirk M Reiter, Raphael Trenker, Leanne M Slater, Phillip J Stansfeld, Ioannis Vakonakis
Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) and Knob-associated Histidine-rich Protein (KAHRP) are directly linked to malaria pathology. PfEMP1 and KAHRP cluster on protrusions (knobs) on the P. falciparum-infected erythrocyte surface and enable pathogenic cytoadherence of infected erythrocytes to the host microvasculature, leading to restricted blood flow, oxygen deprivation and damage of tissues. Here we characterize the interactions of PfEMP1 and KAHRP with host erythrocyte spectrin using biophysical, structural and computational approaches...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28806058/metalloproteases-of-the-inner-mitochondrial-membrane
#2
Roman Levytskyy, Iryna Bohovych, Oleh Khalimonchuk
The inner mitochondrial membrane (IM) is among most protein-rich cellular compartments. The metastable IM sub-proteome where the concentration of proteins is approaching oversaturation creates a challenging protein folding environment with high probability for protein malfunction or aggregation. Failure to maintain protein homeostasis in such a setting can impair functional integrity of the mitochondria and drive clinical manifestations. The IM is equipped with a series of highly conserved, proteolytic complexes dedicated to the maintenance of normal protein homeostasis within this mitochondrial sub-compartment...
August 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28803999/growth-arrest-and-morphological-changes-triggered-by-emodin-on-trypanosoma-cruzi-epimastigotes-cultivated-in-axenic-medium
#3
Ana R De Lima, Karem Noris-Suárez, Antonio Bretaña, Victor T Contreras, Maria C Navarro, Luis Pérez-Ybarra, José Bubis
Emodin is an anthraquinone obtained from Rheum palmatum rootstocks. Here we tested the cytotoxic effects of emodin on Trypanosoma cruzi epimastigotes, as well as the morphological changes that were induced by this compound in the parasite. Emodin was permeable and blocked in vitro cell division of T. cruzi epimastigotes in axenic medium, causing growth arrest in a dose-dependent but reversible manner. Emodin-exposed epimastigotes underwent duplication of organelles, such as the nucleus, kinetoplast and flagellum, but were incapable of completing cytokinesis...
August 10, 2017: Biochimie
https://www.readbyqxmd.com/read/28803731/purification-and-characterization-of-the-colicin-a-immunity-protein-in-detergent-micelles
#4
Ane Metola, Ana M Bouchet, Marian Alonso-Mariño, Tammo Diercks, Lena Mäler, Félix M Goñi, Ana R Viguera
The immunity proteins against pore-forming colicins represent a family of integral membrane proteins that reside in the inner membrane of producing cells. Cai, the colicin A immunity protein, was characterized here in detergent micelles by circular dichroism (CD), size exclusion chromatography, chemical cross-linking, nuclear magnetic resonance (NMR) spectroscopy, cysteine accessibility, and colicin A binding in detergent micelles. Bile-salt derivatives induced extensive protein polymerization that precluded further investigation...
August 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28803135/effects-of-aging-on-basement-membrane-of-the-soleus-muscle-during-recovery-following-disuse-atrophy-in-rats
#5
Yuji Kanazawa, Keisuke Ikegami, Mitsugu Sujino, Satoshi Koinuma, Mamoru Nagano, Yuki Oi, Tomoya Onishi, Shinichi Sugiyo, Isao Takeda, Hiroshi Kaji, Yasufumi Shigeyoshi
Aging is known to lead to the impaired recovery of muscle after disuse as well as the increased susceptibility of the muscle to damage. Here, we show that, in the older rats, reloading after disuse atrophy, causes the damage of the muscle fibers and the basement membrane (BM) that structurally support the muscle fibers. Male Wistar rats of 3-(young) and 20-(older) months of age were subjected to hindlimb-unloading for 2weeks followed by reloading for a week. In the older rats, the soleus muscles showed necrosis and central nuclei fiber indicating the regeneration of muscle fibers...
August 9, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28802158/lipidation-increases-antiviral-activities-of-coronavirus-fusion-inhibiting-peptides
#6
Jung-Eun Park, Tom Gallagher
Coronaviruses (CoVs) can cause life-threatening respiratory diseases. Their infectious entry requires viral spike (S) proteins, which attach to cell receptors, undergo proteolytic cleavage, and then refold in a process that catalyzes virus-cell membrane fusion. Fusion-inhibiting peptides bind to S proteins, interfere with refolding, and prevent infection. Here we conjugated fusion-inhibiting peptides to various lipids, expecting this to secure peptides onto cell membranes and thereby increase antiviral potencies...
August 9, 2017: Virology
https://www.readbyqxmd.com/read/28801553/dead-end-complex-lipid-interactions-and-catalytic-mechanism-of-microsomal-glutathione-transferase-1-an-electron-crystallography-and-mutagenesis-investigation
#7
Qie Kuang, Pasi Purhonen, Johan Ålander, Richard Svensson, Veronika Hoogland, Jens Winerdal, Linda Spahiu, Astrid Ottosson-Wadlund, Caroline Jegerschöld, Ralf Morgenstern, Hans Hebert
Microsomal glutathione transferase 1 (MGST1) is a detoxification enzyme belonging to the Membrane Associated Proteins in Eicosanoid and Glutathione Metabolism (MAPEG) superfamily. Here we have used electron crystallography of two-dimensional crystals in order to determine an atomic model of rat MGST1 in a lipid environment. The model comprises 123 of the 155 amino acid residues, two structured phospholipid molecules, two aliphatic chains and one glutathione (GSH) molecule. The functional unit is a homotrimer centered on the crystallographic three-fold axes of the unit cell...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800364/expression-optimization-of-a-cell-membrane-penetrating-human-papillomavirus-type-16-therapeutic-vaccine-candidate-in-nicotiana-benthamiana
#8
Romana J R Yanez, Renate Lamprecht, Milaid Granadillo, Brandon Weber, Isis Torrens, Edward P Rybicki, Inga I Hitzeroth
High-risk human papillomaviruses (hr-HPVs) cause cervical cancer, the fourth most common cancer in women worldwide. A HPV-16 candidate therapeutic vaccine, LALF32-51-E7, was developed by fusing a modified E7 protein to a bacterial cell-penetrating peptide (LALF): this elicited both tumour protection and regression in pre-clinical immunization studies. In the current study, we investigated the potential for producing LALF32-51-E7 in a plant expression system by evaluating the effect of subcellular localization and usage of different expression vectors and gene silencing suppressors...
2017: PloS One
https://www.readbyqxmd.com/read/28797211/disulfide-bonds-a-key-modification-in-bacterial-extracytoplasmic-proteins
#9
S F Lee, L Davey
Disulfide bonds are a common posttranslational modification that contributes to the folding and stability of extracytoplasmic proteins. Almost all organisms, from eukaryotes to prokaryotes, have evolved enzymes to make and break these bonds. Accurate and efficient disulfide bond formation can be vital for protein function; therefore, the enzymes that catalyze disulfide bond formation are involved in multiple biological processes. Recent advances clearly show that oral bacteria also have the ability to from disulfide bonds, and this ability has an effect on a range of dental plaque-related phenotypes...
August 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28797121/non-alcoholic-fatty-liver-disease-in-mice-with-heterozygous-mutation-in-tmed2
#10
Wenyang Hou, Swati Gupta, Marie-Claude Beauchamp, Libin Yuan, Loydie A Jerome-Majewska
The transmembrane emp24 domain/p24 (TMED) family are essential components of the vesicular transport machinery. Members of the TMED family serve as cargo receptors implicated in selection and packaging of endoplasmic reticulum (ER) luminal proteins into coatomer (COP) II coated vesicles for anterograde transport to the Golgi. Deletion or mutations of Tmed genes in yeast and Drosophila results in ER-stress and activation of the unfolded protein response (UPR). The UPR leads to expression of genes and proteins important for expanding the folding capacity of the ER, degrading misfolded proteins, and reducing the load of new proteins entering the ER...
2017: PloS One
https://www.readbyqxmd.com/read/28793214/influence-of-protein-scaffold-on-side-chain-transfer-free-energies
#11
Dagen C Marx, Karen G Fleming
The process by which membrane proteins fold involves the burial of side chains into lipid bilayers. Both structure and function of membrane proteins depend on the magnitudes of side-chain transfer free energies (ΔΔGsc(o)). In the absence of other interactions, ΔΔGsc(o) is an independent property describing the energetics of an isolated side chain in the bilayer. However, in reality, side chains are attached to the peptide backbone and surrounded by other side chains in the protein scaffold in biology, which may alter the apparent ΔΔGsc(o)...
August 8, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28793212/intrinsically-disordered-stress-protein-cor15a-resides-at-the-membrane-surface-during-dehydration
#12
Anne Bremer, Ben Kent, Thomas Hauß, Anja Thalhammer, Nageshwar R Yepuri, Tamim A Darwish, Christopher J Garvey, Gary Bryant, Dirk K Hincha
Plants from temperate climate zones are able to increase their freezing tolerance during exposure to low, above-zero temperatures in a process termed cold acclimation. During this process, several cold-regulated (COR) proteins are accumulated in the cells. One of them is COR15A, a small, intrinsically disordered protein that contributes to leaf freezing tolerance by stabilizing cellular membranes. The isolated protein folds into amphipathic α-helices in response to increased crowding conditions, such as high concentrations of glycerol...
August 8, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28791383/a-mutation-in-notch1-ligand-binding-region-detected-in-patients-with-oral-squamous-cell-carcinoma-reduces-notch1-oncogenic-effect
#13
Masahiro Uchibori, Ken-Ichi Aoyama, Yoshihide Ota, Kagemasa Kajiwara, Masafumi Tanaka, Minoru Kimura
NOTCH1 is known as an oncogenic or tumor suppressive gene in solid cancer. NOTCH1 mutations in oral squamous cell carcinoma (OSCC) frequently occur near the ligand-binding region. These mutations change the domain structure of this protein and affect the ligand binding activity. When NOTCH1 is activated by ligand binding, NOTCH1 intracellular domain (NICD) is cleaved from the cell membrane. This study investigated the functional change induced by a NOTCH1 mutation detected in OSCC clinical samples using stable transformant analysis...
August 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28791368/two-novel-cross%C3%A2-protective-antigens-for-bovine-pasteurella-multocida
#14
Huihui Du, Chenlu Wu, Chunming Li, Rendong Fang, Jianwei Ma, Jiale Ji, Zhihong Li, Nengzhang Li, Yuanyi Peng, Zeyang Zhou
Pasteurella multocida is an important pathogen that leads to a range of diseases that have severe economic consequences on cattle production. In order to develop an effective cross‑protective component vaccine, an immunoproteomics approach was used to analyze outer membrane proteins (OMPs) of the P. multocida serotype A, B and F strains. Candidate antigen molecules from the whole genome were screened via linear trap quadrupole mass spectrometry and bioinformatics analysis, and the reactogenicity of the candidate antigen molecules was analyzed via cloning, expression, and ELISA or protein immunoblotting, and the vaccine efficacy of the candidate molecules was determined in infective animal models and cross‑protective antigens may be obtained...
August 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28779980/secretion-induces-cell-ph-dynamics-impacting-assembly-disassembly-of-the-fusion-protein-complex-a-combined-fluorescence-and-atomic-force-microscopy-study
#15
REVIEW
Kenneth T Lewis, Akshata R Naik, Suvra S Laha, Sunxi Wang, Guangzhao Mao, Eric Kuhn, Bhanu P Jena
A wide range of cellular activities including protein folding and cell secretion, such as neurotransmission or insulin release, are all governed by intracellular pH homeostasis, underscoring the importance of pH on critical life processes. Nano- scale pH measurements of cells and biomolecules therefore hold great promise in understanding a plethora of cellular functions, in addition to disease detection and therapy. In the current study, a novel approach using cadmium telluride quantum dots (CdTeQDs) as pH sensors, combined with fluorescent imaging, spectrofluorimetry, atomic force microscopy (AFM), and Western blot analysis, enabled the study of intracellular pH dynamics at 1 milli-pH sensitivity and 80nm pixel resolution, during insulin secretion...
August 2, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28779839/efficient-screening-and-optimization-of-membrane-protein-production-in-escherichia-coli
#16
Jacopo Marino, Katharina Holzhüter, Benedikt Kuhn, Eric R Geertsma
Escherichia coli is one of the most widely used expression hosts for membrane proteins. However, establishing conditions for its recombinant production of membrane proteins remains difficult. Attempts to produce membrane proteins frequently result in either no expression or expression as misfolded aggregates. We developed an efficient pipeline for improving membrane protein overexpression in E. coli that is based on two approaches. The first involves transcriptional fusions, small additional RNA sequences upstream of the target open reading frame, to overcome no or poor overall expression levels...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28772071/systemic-delivery-of-folate-peg-sirna-lipopolyplexes-with-enhanced-intracellular-stability-for-in-vivo-gene-silencing-in-leukemia
#17
Dian-Jang Lee, Eva Kessel, Taavi Lehto, Xueying Liu, Naoto Yoshinaga, Kärt Padari, Ying-Chen Chen, Susanne Kempter, Satoshi Uchida, Joachim O Rädler, Margus Pooga, Ming-Thau Sheu, Kazunori Kataoka, Ernst Wagner
Protection of small interfering RNA (siRNA) against degradation and targeted delivery across the plasma and endosomal membranes to the final site of RNA interference are major aims for the development of siRNA therapeutics. Targeting for folate receptor (FR)-expressing tumors, we optimized siRNA polyplexes by co-formulating a folate-PEG-oligoaminoamide (for surface shielding and targeting) with one of three lipo-oligoaminoamides (optionally tyrosine-modified, for optimizing stability and size) to generate ~ 100 nm targeted lipopolyplexes (TLPs), which self-stabilize by cysteine disulfide crosslinks...
August 3, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28771529/an-evolutionarily-conserved-glycine-tyrosine-motif-forms-a-folding-core-in-outer-membrane-proteins
#18
Marcin Michalik, Marcella Orwick-Rydmark, Michael Habeck, Vikram Alva, Thomas Arnold, Dirk Linke
An intimate interaction between a pair of amino acids, a tyrosine and glycine on neighboring β-strands, has been previously reported to be important for the structural stability of autotransporters. Here, we show that the conservation of this interacting pair extends to nearly all major families of outer membrane β-barrel proteins, which are thought to have originated through duplication events involving an ancestral ββ hairpin. We analyzed the function of this motif using the prototypical outer membrane protein OmpX...
2017: PloS One
https://www.readbyqxmd.com/read/28771236/the-cubicon-method-for-concentrating-membrane-proteins-in-the-cubic-mesophase
#19
Pikyee Ma, Dietmar Weichert, Luba A Aleksandrov, Timothy J Jensen, John R Riordan, Xiangyu Liu, Brian K Kobilka, Martin Caffrey
The lipid cubic phase (in meso) method is an important approach for generating crystals and high-resolution X-ray structures of integral membrane proteins. However, as a consequence of instability, it can be impossible-using traditional methods-to concentrate certain membrane proteins and complexes to values suitable for in meso crystallization and structure determination. The cubicon method described here exploits the amphiphilic nature of membrane proteins and their natural tendency to partition preferentially into lipid bilayers from aqueous solution...
September 2017: Nature Protocols
https://www.readbyqxmd.com/read/28770472/vacuole-inducing-compounds-that-disrupt-endolysosomal-trafficking-stimulate-production-of-exosomes-by-glioblastoma-cells
#20
Zehui Li, Nneka E Mbah, William A Maltese
Exosomes are produced from mammalian cells when multivesicular endosomes fuse with the plasma membrane, releasing their intralumenal vesicles. In this study we assessed the effects of MOPIPP, a novel indole-based chalcone, and vacuolin-1, a distinct triazine-based compound, on exosome production in cultured glioblastoma and 293T cells. Both compounds promote vacuolization of late endosome compartments and interfere with trafficking of late endosomes to lysosomes, without significant cytotoxicity. The results show that vacuolated cells treated with these compounds release exosomes with morphologies similar to untreated controls...
August 2, 2017: Molecular and Cellular Biochemistry
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