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Unstructured Proteins

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https://www.readbyqxmd.com/read/28546148/translation-initiation-factor-eif4g1-preferentially-binds-yeast-transcript-leaders-containing-conserved-oligo-uridine-motifs
#1
Boris Zinshteyn, Maria F Rojas Duran, Wendy V Gilbert
Translational control of gene expression plays essential roles in cellular stress responses and organismal development by enabling rapid, selective, and localized control of protein production. Translational regulation depends on context-dependent differences in the protein output of mRNAs, but the key mRNA features that distinguish efficiently translated mRNAs are largely unknown. Here we comprehensively determined the RNA-binding preferences of the initiation factor eIF4G to assess whether this core translation initiation factor has intrinsic sequence preferences that may contribute to preferential translation of specific mRNAs...
May 25, 2017: RNA
https://www.readbyqxmd.com/read/28542210/drosophila-dna-polymerase-theta-utilizes-both-helicase-like-and-polymerase-domains-during-microhomology-mediated-end-joining-and-interstrand-crosslink-repair
#2
Kelly Beagan, Robin L Armstrong, Alice Witsell, Upasana Roy, Nikolai Renedo, Amy E Baker, Orlando Scharer, Mitch McVey
Double strand breaks (DSBs) and interstrand crosslinks (ICLs) are toxic DNA lesions that can be repaired through multiple pathways, some of which involve shared proteins. One of these proteins, DNA Polymerase θ (Pol θ), coordinates a mutagenic DSB repair pathway named microhomology-mediated end joining (MMEJ) and is also a critical component for bypass or repair of ICLs in several organisms. Pol θ contains both polymerase and helicase-like domains that are tethered by an unstructured central region. While the role of the polymerase domain in promoting MMEJ has been studied extensively both in vitro and in vivo, a function for the helicase-like domain, which possesses DNA-dependent ATPase activity, remains unclear...
May 25, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28530826/high-speed-atomic-force-microscopy-reveals-loss-of-nuclear-pore-resilience-as-a-dying-code-in-colorectal-cancer-cells
#3
Mahmoud Shaaban Mohamed, Akiko Kobayashi, Azuma Taoka, Takahiro Watanabe-Nakayama, Yosuke Kikuchi, Masaharu Hazawa, Toshinari Minamoto, Yoshihiro Fukumori, Noriyuki Kodera, Takayuki Uchihashi, Toshio Ando, Richard W Wong
Nuclear pore complexes (NPCs) are the sole turnstile implanted in the nuclear envelope (NE), acting as a central nano-regulator of transport between the cytosol and the nucleus. NPCs consist of ~30 proteins, termed nucleoporins. About one-third of nucleoporins harbour natively unstructured, intrinsically disordered phenylalanine-glycine strings (FG-Nups), which engage in transport selectivity. Because the barriers insert deeply in the NPC, they are nearly inaccessible. Several in vitro barrier models have been proposed; however, the dynamic FG-Nups protein molecules themselves are imperceptible in vivo...
May 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28515062/changes-in-total-energy-intake-and-macronutrient-composition-after-bariatric-surgery-predict-long-term-weight-outcome-findings-from-the-swedish-obese-subjects-sos-study
#4
Noora Kanerva, Ingrid Larsson, Markku Peltonen, Anna-Karin Lindroos, Lena M Carlsson
Background: Approximately 20-30% of obese patients do not achieve successful weight outcomes after bariatric surgery.Objective: We examined whether short-term changes (≤0.5 y postsurgery) in energy intake and macronutrient composition after bariatric surgery could predict 10-y weight change.Design: Participants were recruited from the Swedish Obese Subjects (SOS) study, which was a matched (nonrandomized) prospective trial that compared bariatric surgery with usual care for obese patients. A total of 2010 patients who underwent bariatric surgery were included in the study...
May 17, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28507157/translation-and-folding-of-single-proteins-in-real-time
#5
Florian Wruck, Alexandros Katranidis, Knud H Nierhaus, Georg Büldt, Martin Hegner
Protein biosynthesis is inherently coupled to cotranslational protein folding. Folding of the nascent chain already occurs during synthesis and is mediated by spatial constraints imposed by the ribosomal exit tunnel as well as self-interactions. The polypeptide's vectorial emergence from the ribosomal tunnel establishes the possible folding pathways leading to its native tertiary structure. How cotranslational protein folding and the rate of synthesis are linked to a protein's amino acid sequence is still not well defined...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28497950/deamidation-slows-curli-amyloid-protein-aggregation
#6
Hanliu Wang, Qin Shu, Carl Frieden, Michael L Gross
Non-enzymatic deamidation of asparagine and glutamine in peptides and proteins is a frequent modification both in vivo and in vitro. The biological effect is not completely understood, but it is often associated with protein degradation and loss of biological function. Here we describe the deamidation of CsgA, the major protein subunit of curli, which are important proteinaceous components of biofilms. CsgA has a high content of Asn and Gln, a feature seen in other proteins that self-aggregate. We have implemented an approach to monitor deamidation rapidly by following the globally centroid mass shift, providing guidance for studies at the residue level...
May 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28497697/synthetic-protein-scaffolds-for-biosynthetic-pathway-colocalization-on-lipid-droplet-membranes
#7
Jyun-Liang Lin, Jie Zhu, Ian Wheeldon
Eukaryotic biochemistry is organized throughout the cell in and on membrane-bound organelles. When engineering metabolic pathways this organization is often lost, resulting in flux imbalance and a loss of kinetic advantages from enzyme colocalization and substrate channeling. Here, we develop a protein-based scaffold for colocalizing multienzyme pathways on the membranes of intracellular lipid droplets. Scaffolds based on the plant lipid droplet protein oleosin and cohesin-dockerin interaction pairs recruited upstream enzymes in yeast ester biosynthesis to the native localization of the terminal reaction step, alcohol-O-acetyltransferase (Atf1)...
May 23, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28493957/ezrin-interacts-with-s100a4-via-both-its-n-and-c-terminal-domains
#8
Beáta Biri-Kovács, Bence Kiss, Henrietta Vadászi, Gergő Gógl, Gyula Pálfy, György Török, László Homolya, Andrea Bodor, László Nyitray
Ezrin belongs to the ERM (ezrin, radixin, moesin) protein family that has a role in cell morphology changes, adhesion and migration as an organizer of the cortical cytoskeleton by linking actin filaments to the apical membrane of epithelial cells. It is highly expressed in a variety of human cancers and promotes metastasis. Members of the Ca2+-binding EF-hand containing S100 proteins have similar pathological properties; they are overexpressed in cancer cells and involved in metastatic processes. In this study, using tryptophan fluorescence and stopped-flow kinetics, we show that S100A4 binds to the N-terminal ERM domain (N-ERMAD) of ezrin with a micromolar affinity...
2017: PloS One
https://www.readbyqxmd.com/read/28486788/the-long-unstructured-region-of-bcl-xl-modulates-its-structural-dynamics
#9
Prerna Priya, Atanu Maity, Shubhra Ghosh Dastidar
Bcl-xl protein has a long unstructured loop attached to its structured region which joins two helices. The necessity to have this unstructured segment in Bcl-xl is not yet understood. To what extent the unstructured segment can influence the dynamics of the structured region of protein, with potential to influence the function, has been investigated in this work. Molecular dynamics simulation and principal component analysis show how the loop affects the internal motions of the protein, particularly its ligand binding pocket...
May 9, 2017: Proteins
https://www.readbyqxmd.com/read/28481930/expression-of-human-bcl-xl-ser49-and-ser62-mutants-in-caenorhabditis-elegans-causes-germline-defects-and-aneuploidy
#10
Prasamit Saurav Baruah, Myriam Beauchemin, J Alexander Parker, Richard Bertrand
An interesting feature of Bcl-xL protein is the presence of an unstructured loop domain between α1 and α2 helices, a domain not essential for its anti-apoptotic function and absent in CED-9 protein. Within this domain, Bcl-xL undergoes dynamic phosphorylation and dephosphorylation at Ser49 and Ser62 during G2 and mitosis in human cells. Studies have revealed that when these residues are mutated, cells harbour mitotic defects, including chromosome mis-attachment, lagging, bridging and mis-segregation with, ultimately, chromosome instability and aneuploidy...
2017: PloS One
https://www.readbyqxmd.com/read/28471097/synthesis-of-intrinsically-disordered-fluorinated-peptides-for-modular-design-of-high-signal-19-f-mri-agents
#11
Steven E Kirberger, Sofia D Maltseva, Joseph C Manulik, Samuel A Einstein, Bradley P Weegman, Michael Garwood, William C K Pomerantz
(19) F MRI is valuable for in vivo imaging due to the only trace amounts of fluorine in biological systems. Because of the low sensitivity of MRI however, designing new fluorochemicals remains a significant challenge for achieving sufficient (19) F signal. Here, we describe a new class of high-signal, water-soluble fluorochemicals as (19) F MRI imaging agents. A polyamide backbone is used for tuning the proteolytic stability to avoid retention within the body, which is a limitation of current state-of-the-art perfluorochemicals...
June 1, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28454764/ribosomal-proteins-as-documents-of-the-transition-from-unstructured-poly-peptides-to-folded-proteins
#12
REVIEW
Andrei N Lupas, Vikram Alva
For the most part, contemporary proteins can be traced back to a basic set of a few thousand domain prototypes, many of which were already established in the Last Universal Common Ancestor of life on Earth, around 3.5 billion years ago. The origin of these domain prototypes, however, remains poorly understood. One hypothesis posits that they arose from an ancestral set of peptides, which acted as cofactors of RNA-mediated catalysis and replication. Initially, these peptides were entirely dependent on the RNA scaffold for their structure, but as their complexity increased, they became able to form structures by excluding water through hydrophobic contacts, making them independent of the RNA scaffold...
April 26, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28454736/a-new-cryptic-host-defense-peptide-identified-in-human-11-hydroxysteroid-dehydrogenase-1-%C3%AE-like-from-in-silico-identification-to-experimental-evidence
#13
A Bosso, L Pirone, R Gaglione, K Pane, A Del Gatto, L Zaccaro, S Di Gaetano, D Diana, R Fattorusso, E Pedone, V Cafaro, H P Haagsman, A van Dijk, M R Scheenstra, A Zanfardino, O Crescenzi, A Arciello, M Varcamonti, E J A Veldhuizen, A Di Donato, E Notomista, E Pizzo
BACKGROUND: Host defence peptides (HDPs) are evolutionarily conserved components of innate immunity. Human HDPs, produced by a variety of immune cells of hematopoietic and epithelial origin, are generally grouped into two families: beta structured defensins and variably-structured cathelicidins. We report the characterization of a very promising cryptic human HDP, here called GVF27, identified in 11-hydroxysteroid dehydrogenase-1 β-like protein. METHODS: Conformational analysis of GVF27 and its propensity to bind endotoxins were performed by NMR, Circular Dichroism, Fluorescence and Dynamic Light Scattering experiments...
April 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28451587/the-interplay-of-cofactor-interactions-and-post-translational-modifications-in-the-regulation-of-the-aaa-atpase-p97
#14
REVIEW
Petra Hänzelmann, Hermann Schindelin
The hexameric type II AAA ATPase (ATPase associated with various activities) p97 (also referred to as VCP, Cdc48, and Ter94) is critically involved in a variety of cellular activities including pathways such as DNA replication and repair which both involve chromatin remodeling, and is a key player in various protein quality control pathways mediated by the ubiquitin proteasome system as well as autophagy. Correspondingly, p97 has been linked to various pathophysiological states including cancer, neurodegeneration, and premature aging...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28448138/the-idp-specific-force-field-ff14idpsff-improves-the-conformer-sampling-of-intrinsically-disordered-proteins
#15
Dong Song, Ray Luo, Hai-Feng Chen
Intrinsically disordered proteins (IDPs) or intrinsically disordered regions do not have a fixed tertiary structure but play key roles in signal regulation, molecule recognition, and drug targeting. However, it is difficult to study the structure and function of IDPs by traditional experimental methods because of their diverse conformations. Limitations of current generic protein force fields and solvent models were reported in the previous simulations of IDPs. We have also explored overcoming these limitations by developing the ff99IDPs and ff14IDPs force fields to correct the dihedral distribution for eight disorder-promoting residues often observed in IDPs and found encouraging improvements...
May 4, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28432632/tryptophan-fluorescence-yields-and-lifetimes-as-a-probe-of-conformational-changes-in-human-glucokinase
#16
Bogumil Zelent, Chris Bialas, Ignacy Gryczynski, Pan Chen, Rahul Chib, Karina Lewerissa, Maria G Corradini, Richard D Ludescher, Jane M Vanderkooi, Franz M Matschinsky
Five variants of glucokinase (ATP-D-hexose-6-phosphotransferase, EC 2.7.1.1) including wild type and single Trp mutants with the Trp residue at positions 65, 99, 167 and 257 were prepared. The fluorescence of Trp in all locations studied showed intensity changes when glucose bound, indicating that conformational change occurs globally over the entire protein. While the fluorescence quantum yield changes upon glucose binding, the enzyme's absorption spectra, emission spectra and fluorescence lifetimes change very little...
April 22, 2017: Journal of Fluorescence
https://www.readbyqxmd.com/read/28427262/melting-proteins-evidence-for-multiple-stable-structures-upon-thermal-denaturation-of-native-ubiquitin-from-ion-mobility-spectrometry-mass-spectrometry-measurements
#17
Tarick J El-Baba, Daniel W Woodall, Shannon A Raab, Daniel R Fuller, Arthur Laganowsky, David H Russell, David E Clemmer
Ion mobility and mass spectrometry techniques are coupled with a temperature-controlled electrospray ionization source to follow the structural transitions of ubiquitin in aqueous solution (pH = 3) at elevated solution temperatures (T = 26-96 °C). Changes in the charge state distribution are consistent with a two-state, cooperative unfolding transition having a melting temperature of Tm = 71 ± 2 °C, in agreement with prior measurements [ Wintrode , P. L. ; Makhatadze , G. I. ; Privalov , P. L. Proteins , 1994 , 18 , 246 - 253 ]...
April 26, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28404644/preprotein-mature-domains-contain-translocase-targeting-signals-that-are-essential-for-secretion
#18
Katerina E Chatzi, Marios Frantzeskos Sardis, Alexandra Tsirigotaki, Marina Koukaki, Nikolina Šoštarić, Albert Konijnenberg, Frank Sobott, Charalampos G Kalodimos, Spyridoula Karamanou, Anastassios Economou
Secretory proteins are only temporary cytoplasmic residents. They are typically synthesized as preproteins, carrying signal peptides N-terminally fused to their mature domains. In bacteria secretion largely occurs posttranslationally through the membrane-embedded SecA-SecYEG translocase. Upon crossing the plasma membrane, signal peptides are cleaved off and mature domains reach their destinations and fold. Targeting to the translocase is mediated by signal peptides. The role of mature domains in targeting and secretion is unclear...
May 1, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28393136/development-of-%C3%AE-hairpin-peptides-for-the-measurement-of-scf-family-e3-ligase-activity-in-vitro-via-ornithine-ubiquitination
#19
Kaiulani M Houston, Adam T Melvin, Gregery S Woss, Effrat L Fayer, Marcey L Waters, Nancy L Allbritton
Regulation of the ubiquitin-proteasome system (UPS) to treat select types of cancer has become a popular area of drug discovery research. The FDA approval of proteasome inhibitors Bortezomib and Carfilzomib in the treatment of multiple myeloma has led to an increased need for chemical reporters capable of detecting and quantifying protein ubiquitination and the activity of members of the UPS including E3 ubiquitin ligases and the proteasome in the tumor cells of the patients. One limitation of peptide-based reporters is their rapid degradation in the cellular environment by cytosolic peptidases...
March 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28391594/the-functional-roles-of-the-unstructured-n-and-c-terminal-regions-in-%C3%AE-b-crystallin-and-other-mammalian-small-heat-shock-proteins
#20
John A Carver, Aidan B Grosas, Heath Ecroyd, Roy A Quinlan
Small heat-shock proteins (sHsps), such as αB-crystallin, are one of the major classes of molecular chaperone proteins. In vivo, under conditions of cellular stress, sHsps are the principal defence proteins that prevent large-scale protein aggregation. Progress in determining the structure of sHsps has been significant recently, particularly in relation to the conserved, central and β-sheet structured α-crystallin domain (ACD). However, an understanding of the structure and functional roles of the N- and C-terminal flanking regions has proved elusive mainly because of their unstructured and dynamic nature...
April 8, 2017: Cell Stress & Chaperones
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