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membrane protein folding

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https://www.readbyqxmd.com/read/29139344/aeropyrum-pernix-membrane-topology-of-protein-vkor-promotes-protein-disulfide-bond-formation-in-two-subcellular-compartments
#1
Stijntje Hibender, Cristina Landeta, Mehmet Berkmen, Jon Beckwith, Dana Boyd
Disulfide bonds confer stability and activity to proteins. Bioinformatic approaches allow predictions of which organisms make protein disulfide bonds and in which subcellular compartments disulfide bond formation takes place. Such an analysis, along with biochemical and protein structural data, suggests that many of the extremophile Crenarachaea make protein disulfide bonds in both the cytoplasm and the cell envelope. We have sought to determine the oxidative folding pathways in the sequenced genomes of the Crenarchaea, by seeking homologues of the enzymes known to be involved in disulfide bond formation in bacteria...
November 15, 2017: Microbiology
https://www.readbyqxmd.com/read/29138096/one-single-salt-bridge-explains-the-different-cytolytic-activities-shown-by-actinoporins-sticholysin-i-and-ii-from-the-venom-of-stichodactyla-helianthus
#2
Esperanza Rivera-de-Torre, Juan Palacios-Ortega, Sara García-Linares, José G Gavilanes, Álvaro Martínez-Del-Pozo
Sticholysins I and II (StnI and StnII), α-pore forming toxins from the sea anemone Stichodactyla helianthus, are water-soluble toxic proteins which upon interaction with lipid membranes of specific composition bind to the bilayer, extend and insert their N-terminal α-helix, and become oligomeric integral membrane structures. The result is a pore that leads to cell death by osmotic shock. StnI and StnII show 93% of sequence identity, but also different membrane pore-forming activities. The hydrophobicity profile along the first 18 residues revealed differences which were canceled by substituting StnI amino acids 2 and 9...
November 11, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29137479/the-role-of-the-carbohydrates-in-plasmatic-membrane
#3
P Sprovieri, G Martino
In the following paper, authors describe glycans present on cell membranes as they affect the folding, the spatial arrangement, the behavior and the interaction with the substrate of some membrane proteins. Authors describe the synthesis and assembly of a glycan on a protein, the formation of N-glycans, the maturation of an N-glycan in different cellular compartments, the structure of the glycocalyx and how it interacts with any pathogens. The study of the E-cadherin and the potassium channel to demonstrate how glycans affect the spatial arrangement, the stability and activity of the glycoproteins on the membranes...
November 10, 2017: Physiological Research
https://www.readbyqxmd.com/read/29135937/relax-cool-down-and-scaffold-how-to-restore-surface-expression-of-folding-deficient-mutant-gpcrs-and-slc6-transporters
#4
REVIEW
H M Mazhar Asjad, Shahrooz Nasrollahi-Shirazi, Sonja Sucic, Michael Freissmuth, Christian Nanoff
Many diseases arise from mutations, which impair protein folding. The study of folding-deficient variants of G protein-coupled receptors and solute carrier 6 (SLC6) transporters has shed light on the folding trajectory, how it is monitored and how misfolding can be remedied. Reducing the temperature lowers the energy barrier between folding intermediates and thereby eliminates stalling along the folding trajectory. For obvious reasons, cooling down is not a therapeutic option. One approach to rescue misfolded variants is to use membrane-permeable orthosteric ligands...
November 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29133410/unprecedented-pathway-of-reducing-equivalents-in-a-diflavin-linked-disulfide-oxidoreductase
#5
Rubén M Buey, Juan B Arellano, Luis López-Maury, Sergio Galindo-Trigo, Adrián Velázquez-Campoy, José L Revuelta, José M de Pereda, Francisco J Florencio, Peter Schürmann, Bob B Buchanan, Monica Balsera
Flavoproteins participate in a wide variety of physiologically relevant processes that typically involve redox reactions. Within this protein superfamily, there exists a group that is able to transfer reducing equivalents from FAD to a redox-active disulfide bridge, which further reduces disulfide bridges in target proteins to regulate their structure and function. We have identified a previously undescribed type of flavin enzyme that is exclusive to oxygenic photosynthetic prokaryotes and that is based on the primary sequence that had been assigned as an NADPH-dependent thioredoxin reductase (NTR)...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29133296/comparison-of-preservation-and-transportation-protocols-for-preloaded-descemet-membrane-endothelial-keratoplasty
#6
Vito Romano, Mohit Parekh, Alessandro Ruzza, Colin E Willoughby, Stefano Ferrari, Diego Ponzin, Stephen B Kaye, Hannah J Levis
BACKGROUND/AIMS: Descemet membrane endothelial keratoplasty (DMEK) preparation is technically demanding and is a limiting factor for uptake of this kind of surgery. Supply methods that simplify the procedure for surgeons are key to increasing uptake. This study compares two different shipping protocols for DMEK. METHODS: An 8.5 mm DMEK graft was punched, marked and loaded for transportation in two different conditions: (A) endothelium trifolded inwards in organ culture conditions (n=7) and (B) endothelium rolled outwards in hypothermic conditions (n=7)...
November 13, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/29133260/expression-of-fshr-in-chondrocytes-and-the-effect-of-fsh-on-chondrocytes
#7
Dehuan Kong, Qingbo Guan, Guandong Li, Wei Xin, Xiaoyi Qi, Yanjing Guo, Jiajun Zhao, Jin Xu, Shui Sun, Ling Gao
OBJECTIVE: Chondrocytes express many kinds of hormone receptors. The function of Follicle stimulating hormone (FSH) in the ovary is mediated by FSH receptor (FSHR). FSH receptor (FSHR) is found in many non-ovarian tissues, however it has been unclear if chondrocytes express FSHR. The purpose of this study is to determine it. METHODS: Mouse primary chondrocytes and human articular cartilage tissues were examined. The expression and sequence of FSHR mRNA by reverse transcription polymerase chain reaction (RT-PCR) and sequenced, respectively, and its protein expression was tested using western blotting and location was observed under immunofluorescence microscopy...
November 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29131519/displaying-tetra-membrane-spanning-claudins-on-enveloped-virus-like-particles-for-cancer-immunotherapy
#8
Irene C Schneider, Jessica Hartmann, Gundula Braun, Jörn Stitz, Thorsten Klamp, Mahjoub Bihi, Ugur Sahin, Christian J Buchholz
Virus-like particles (VLPs) displaying foreign antigens have become an important tool in vaccination including the induction of immune responses against self-antigens. Claudin 6 (CLDN6) has been identified as tumor-associated antigen and is therefore a potential target for tumor vaccination strategies. However, as tetra-membrane spanning protein its incorporation into VLPs while preserving a native fold is challenging. Here, we attempted the incorporation of a panel of engineered CLDN6 variants into the membrane of retrovirus-derived VLPs...
November 13, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/29129383/the-structure-of-a-conserved-domain-of-tamb-reveals-a-hydrophobic-%C3%AE-taco-fold
#9
Inokentijs Josts, Christopher James Stubenrauch, Grishma Vadlamani, Khedidja Mosbahi, Daniel Walker, Trevor Lithgow, Rhys Grinter
The translocation and assembly module (TAM) plays a role in the transport and insertion of proteins into the bacterial outer membrane. TamB, a component of this system spans the periplasmic space to engage with its partner protein TamA. Despite efforts to characterize the TAM, the structure and mechanism of action of TamB remained enigmatic. Here we present the crystal structure of TamB amino acids 963-1,138. This region represents half of the conserved DUF490 domain, the defining feature of TamB. TamB963-1138 consists of a concave, taco-shaped β sheet with a hydrophobic interior...
November 3, 2017: Structure
https://www.readbyqxmd.com/read/29128595/ultrafast-protein-folding-in-membrane-mimetic-environments
#10
Georg Krainer, Andreas Hartmann, Abhinaya Anandamurugan, Pablo Gracia, Sandro Keller, Michael Schlierf
Proteins fold on timescales from hours to microseconds. In addition to protein size, sequence, and topology, the environment represents an equally important factor in determining folding speed. This is particularly relevant for proteins that require a lipid membrane or a membrane mimic to fold. However, only little is known about how properties of such a hydrophilic/hydrophobic interface modulate the folding landscape of membrane-interacting proteins. Here, we studied the influence of different membrane-mimetic micellar environments on the folding and unfolding kinetics of the helical-bundle protein Mistic...
November 8, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29128310/position-specific-contribution-of-interface-tryptophans-on-membrane-protein-energetics
#11
Deepti Chaturvedi, Radhakrishnan Mahalakshmi
Interface tryptophans are key residues that facilitate the folding and stability of membrane proteins. Escherichia coli OmpX possesses two unique interface tryptophans, namely Trp76, which is present at the interface and is solvent-exposed, and Trp140, which is relatively more lipid solvated than Trp76 in symmetric lipid membranes. Here, we address the requirement for tryptophan and the consequences of aromatic amino acid substitutions on the folding and stability of OmpX. Using spectroscopic measurements of OmpX-Trp/Tyr/Phe mutants, we show that the specific mutation W76→Y allows barrel assembly >1...
November 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29125808/monocyte-derived-procoagulant-microvesicles-induced-by-high-glucose-can-be-attenuated-by-the-antioxidant-n-acetyl-l-cysteine-partly-through-the-p38-mapk-pathway
#12
Mingzhen Li, Xiao Zhang, Jing Yu, Xin Wu, Lirong Sun
BACKGROUND: Microvesicles (MVs) are small membrane vesicles that are derived from many different cell types by a process of exocytic budding of the plasma membrane. MVs may be associated with a higher incidence of vascular disease in diabetic patients, but the mechanism of this association is unclear. Diabetic patients also show hypercoagulability and platelet hyperaggregability. In this study, we investigated the generation and activity of high glucose (HG)-induced MVs from monocytes to elucidate the potential mechanism of such MVs in diabetes...
November 10, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/29123984/transmembrane-thioredoxin-related-protein-tmx1-is-reversibly-oxidized-in-response-to-protein-accumulation-in-the-endoplasmic-reticulum
#13
Yoshiyuki Matsuo, Kiichi Hirota
Numerous secretory and membrane proteins undergo post-translational modifications in the endoplasmic reticulum (ER), and the formation of disulfide bonds is a modification that is critical for proper protein folding. The mammalian ER contains a large family of oxidoreductases that are considered to catalyze thiol/disulfide exchange and ensure the maintenance of a redox environment within the ER. Disruption of ER homeostasis causes an accumulation of misfolded and unfolded proteins, a condition termed ER stress...
November 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29121705/reactive-oxygen-species-depletion-by-silibinin-stimulates-apoptosis-like-death-in-escherichia-coli
#14
Bin Lee, Dong Gun Lee
Silibinin is the major active component of silymarin, extracted from medicinal plant Silybum marianum. Silibinin has potent antibacterial activity; however, the exact mechanism underlying its activity has not been elucidated. Here, we investigated the novel mechanism of silibinin against Escherichia coli. Time-kill kinetic assay showed that silibinin possess a bactericidal effect at minimal inhibitory concentration (MIC) and higher concentrations (two and four-fold MIC). At the membrane depolarization and increased intracellular Ca²⁺ levels were observed, considered as characteristics of bacterial apoptosis...
November 9, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29119969/tumor-targeting-efficacy-of-a-bf211-prodrug-through-hydrolysis-by-fibroblast-activation-protein-%C3%AE
#15
Xiao-Ping Chai, Guang-Long Sun, Yan-Fen Fang, Li-Hong Hu, Xuan Liu, Xiong-Wen Zhang
BF211, a bufalin (BF) derivative, exhibits stronger anti-cancer activity than BF but with potential cardiotoxicity. Fibroblast activation protein-α (FAPα) is a membrane-bound protease specifically expressed by carcinoma-associated fibroblasts, thus has been used for the selective delivery of anticancer agents. In this study, we used a FAPα-based prodrug strategy to synthesize a dipeptide (Z-Gly-Pro)-conjugated BF211 prodrug named BF211-03. BF211-03 was hydrolyzed by recombinant human FAPα (rhFAPα) and cleaved by homogenates of human colon cancer HCT-116 or human gastric cancer MGC-803 xenografts...
November 9, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29118124/c-myc-represses-transcription-of-the-epstein-barr-virus-latent-membrane-protein-1-early-after-primary-b-cell-infection
#16
Alexander M Price, Joshua E Messinger, Micah A Luftig
Recent evidence has shown that the EBV oncogene LMP1 is not expressed at high levels early after EBV-infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased fifty-fold between seven days post infection and the LCL state. Metabolic labeling of nascently transcribed mRNA indicated this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29117500/development-and-ultrastructure-of-the-rigid-dorsal-and-flexible-ventral-cuticles-of-the-elytron-of-the-red-flour-beetle-tribolium-castaneum
#17
Mi Young Noh, Subbaratnam Muthukrishnan, Karl J Kramer, Yasuyuki Arakane
Insect exoskeletons are composed of the cuticle, a biomaterial primarily formed from the linear and relatively rigid polysaccharide, chitin, and structural proteins. This extracellular material serves both as a skin and skeleton, protecting insects from environmental stresses and mechanical damage. Despite its rather limited compositional palette, cuticles in different anatomical regions or developmental stages exhibit remarkably diverse physicochemical and mechanical properties because of differences in chemical composition, molecular interactions and morphological architecture of the various layers and sublayers throughout the cuticle including the envelope, epicuticle and procuticle (exocuticle and endocuticle)...
November 5, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29114023/mcr-1-inhibition-with-peptide-conjugated-phosphorodiamidate-morpholino-oligomers-restores-sensitivity-to-polymyxin-in-escherichia-coli
#18
Seth M Daly, Carolyn R Sturge, Christina F Felder-Scott, Bruce L Geller, David E Greenberg
In late 2015, the first example of a transferrable polymyxin resistance mechanism in Gram-negative pathogens, MCR-1, was reported. Since that report, MCR-1 has been described to occur in many Gram-negative pathogens, and the mechanism of MCR-1-mediated resistance was rapidly determined: an ethanolamine is attached to lipid A phosphate groups, rendering the membrane more electropositive and repelling positively charged polymyxins. Acquisition of MCR-1 is clinically significant because polymyxins are frequently last-line antibiotics used to treat extensively resistant organisms, so acquisition of this mechanism might lead to pan-resistant strains...
November 7, 2017: MBio
https://www.readbyqxmd.com/read/29111118/hsp90-and-thioredoxin-thioredoxin-reductase-enable-the-catalytic-activity-of-clostridial-neurotoxins-inside-nerve-terminals
#19
Marco Pirazzini, Domenico Azarnia Tehran, Giulia Zanetti, Ornella Rossetto, Cesare Montecucco
Botulinum (BoNTs) and tetanus (TeNT) neurotoxins are the most toxic substances known and form the growing family of Clostridial neurotoxins (CNT), the etiologic agents of botulism and tetanus. CNT are composed of a metalloprotease light chain (L), linked via a disulfide bond to a heavy chain (H). H mediates the binding to nerve terminals and the membrane translocation of L into the cytosol, where its substrates, the three SNARE proteins, are localized. L translocation is accompanied by unfolding and, once delivered on the cytosolic side of the endosome membrane, it has to be reduced and reacquire the native fold to be active...
October 27, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29110486/impact-of-detergents-on-membrane-protein-complex-isolation
#20
Yu-Chen Lee, Jenny Arnling Bååth, Ryan M Bastle, Sonali Bhattacharjee, Mary Jo Cantoria, Mark Dornan, Enrique Gamero-Estevez, Lenzie Ford, Lenka Halova, Jennifer Kernan, Charlotte Kürten, Siran Li, Jerahme Martinez, Nalani Sachan, Medoune Sarr, Xiwei Shan, Nandhitha Subramanian, Keith Rivera, Darryl Pappin, Sue-Hwa Lin
Detergents play an essential role during the isolation of membrane protein complexes. Inappropriate use of detergents may affect the native fold of the membrane proteins, their binding to antibodies, or their interaction with partner proteins. Here we used cadherin-11 (Cad11) as an example to examine the impact of detergents on membrane protein complex isolation. We found that mAb 1A5 could immunoprecipitate Cad11 when membranes were solubilized by dodecyl maltoside (DDM) but not by octylglucoside, suggesting that octylglucoside interferes with Cad11-mAb 1A5 interaction...
November 13, 2017: Journal of Proteome Research
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