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Intrinsically disordered

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https://www.readbyqxmd.com/read/29334167/cross-linking-mass-spectrometry-for-studying-protein-structures-and-protein-protein-interactions-where-are-we-now-and-where-should-we-go-from-here
#1
Andrea Sinz
Structural mass spectrometry (MS) is gaining increasing importance in deriving valuable three-dimensional structural information on proteins and protein complexes and complements existing techniques, such as NMR spectroscopy and X-ray crystallography. Structural MS unites different MS-based techniques, i.e, hydrogen-deuterium exchange, native MS, ion-mobility MS, protein footprinting, and chemical cross-linking/MS, and allows fundamental questions in structural biology to be addressed. In this article, I will focus on the cross-linking/MS strategy...
January 15, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29332398/high-performance-thermoelectric-bulk-colusite-by-process-controlled-structural-disordering
#2
Cédric Bourgès, Yohan Bouyrie, Andrew R Supka, Rabih Al Rahal Al Orabi, Pierric Lemoine, O I Lebedev, Michihiro Ohta, Koichiro Suekuni, Vivian Nassif, Vincent Hardy, Ramzy Daou, Yuzuru Miyazaki, Marco Fornari, Emmanuel Guilmeau
High-performance thermoelectric bulk sulfide with the colusite structure is achieved by controlling the densification process and forming short-to-medium range structural defects. A simple and powerful way to adjust carrier concentration combined with enhanced phonon scattering through point defects and disordered regions is described. By combining experiments with band structure and phonons calculations, we elucidate, for the first time, the underlying mechanism at the origin of intrinsically low thermal conductivity in colusite samples as well as the effect of S vacancies and antisite defects on the carrier concentration...
January 14, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29331721/understanding-protein-drug-interactions-using-ion-mobility-mass-spectrometry
#3
REVIEW
Claire E Eyers, Matthias Vonderach, Samantha Ferries, Kiani Jeacock, Patrick A Eyers
Ion mobility-mass spectrometry (IM-MS) is an important addition to the analytical toolbox for the structural evaluation of proteins, and is enhancing many areas of biophysical analysis. Disease-associated proteins, including enzymes such as protein kinases, transcription factors exemplified by p53, and intrinsically disordered proteins, including those prone to aggregation, are all amenable to structural analysis by IM-MS. In this review we discuss how this powerful technique can be used to understand protein conformational dynamics and aggregation pathways, and in particular, the effect that small molecules, including clinically-relevant drugs, play in these processes...
January 10, 2018: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29330519/large-scale-aggregation-analysis-of-eukaryotic-proteins-reveals-an-involvement-of-intrinsically-disordered-regions-in-protein-folding
#4
Eri Uemura, Tatsuya Niwa, Shintaro Minami, Kazuhiro Takemoto, Satoshi Fukuchi, Kodai Machida, Hiroaki Imataka, Takuya Ueda, Motonori Ota, Hideki Taguchi
A subset of the proteome is prone to aggregate formation, which is prevented by chaperones in the cell. To investigate whether the basic principle underlying the aggregation process is common in prokaryotes and eukaryotes, we conducted a large-scale aggregation analysis of ~500 cytosolic budding yeast proteins using a chaperone-free reconstituted translation system, and compared the obtained data with that of ~3,000 Escherichia coli proteins reported previously. Although the physicochemical properties affecting the aggregation propensity were generally similar in yeast and E...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330047/an-intrinsically-disordered-domain-in-polaribacter-irgensii-kopri-22228-cspb-confers-extraordinary-freeze-tolerance
#5
Youn Hong Jung, Ji-Hyun Uh, Kyunghee Lee, Hana Im
Organisms living in extremely cold environments possess mechanisms to survive low temperatures. Among the known cold-induced genes, cold-shock proteins (Csps) are the most prominent. A csp-homologous gene, cspBPi, has been cloned from the Arctic bacterium Polaribacter irgensii KOPRI 22228, and overexpression of this gene greatly increased the freezing tolerance of its host. This protein consists of a unique N-terminal domain and a well conserved C-terminal cold shock domain. To elucidate the detailed mechanisms involved in the extraordinary freeze-tolerance conferred by CspBPi, we identified the responsible domain by mutational analysis...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29330035/harmine-enhances-gabaergic-transmission-onto-basoamygdala-projection-neurons-in-mice
#6
Wei-Zhu Liu, Bo-Wei Huang, Wen-Jie You, Ping Hu, Xue-Hui Wang, Jun-Yu Zhang, Xiao-Bin Xu, Zong-Yong Zhang, Bing-Xing Pan, Wen-Hua Zhang
Emerging evidence indicates that loss of inhibitory tone in amygdala with its subsequent overactivation contributes to the development of multiple mental disorders such as anxiety disorders and post-traumatic stress disorder (PTSD). Harmine is a member of natural β-carboline alkaloids which can readily cross the blood brain barrier and displays significant antidepressant and anxiolytic effects in rodents. However, the underlying neurobiological mechanisms are largely unknown. Here, by using whole-cell patch clamp recordings in in vitro amygdala slices, we examined the effect of harmine on glutamatergic and GABAergic transmission onto basal amygdala (BA) projection neurons (PNs)...
January 9, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29329397/minar1-is-a-notch2-binding-protein-that-inhibits-angiogenesis-and-breast-cancer-growth
#7
Rachel Xi-Yeen Ho, Rosana D Meyer, Kevin B Chandler, Esma Ersoy, Michael Park, Philip A Bondzie, Nima Rahimi, Huihong Xu, Catherine E Costello, Nader Rahimi
Intrinsically disordered proteins (IDPs)/intrinsically unstructured proteins (IUPs) are characterized by the lack of fixed or stable tertiary structure, and are increasingly recognized as an important class of proteins with major roles in signal transduction and transcriptional regulation. In this study, we report the identification and functional characterization of a previously uncharacterized protein (UPF0258/KIAA1024), major intrinsically disordered Notch2-associated receptor 1 (MINAR1). While MINAR1 carries a single transmembrane domain and a short cytoplasmic domain, it has a large extracellular domain that shares no similarity with known protein sequences...
January 10, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29327340/shank3-deficient-thalamocortical-neurons-show-hcn-channelopathy-and-alterations-in-intrinsic-electrical-properties
#8
Mengye Zhu, VinayKumar Idikuda, Jianbing Wang, Fusheng Wei, Virang Kumar, Nikhil Shah, Christopher B Waite, Qinglian Liu, Lei Zhou
Shank3 is a scaffolding protein that is highly enriched in excitatory synapses. Mutations in Shank3 gene have been linked to neuropsychiatric disorders especially the Autism Spectrum Disorders (ASD). Shank3 deficiency is known to cause impairments in synaptic transmission, but its effects on basic neuronal electrical properties that are more localized to the soma and proximal dendrites remain unclear. Here we confirmed that in heterologous expression systems two different Shank3 isoforms, Shank3A and Shank3C, significant increase the surface expression of the hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channel...
January 12, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29326986/measles-virus-background-and-oncolytic-virotherapy
#9
REVIEW
Sankhajit Bhattacharjee, Pramod Kumar Yadava
Measles is a highly transmissible disease caused by measles virus and remains a major cause of child mortality in developing countries. Measles virus nucleoprotein (N) encapsidates the RNA genome of the virus for providing protection from host cell endonucleases and for specific recognition of viral RNA as template for transcription and replication. This protein is over-expressed at the time of viral replication. The C-terminal of N protein is intrinsically disordered, which enables this protein to interact with several host cell proteins...
March 2018: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29323485/spark-plasma-sintering-sps-assisted-synthesis-and-thermoelectric-characterization-of-magn%C3%A3-li-phase-v6o11
#10
Markus Joos, Giacomo Cerretti, Igor Veremchuk, Patrick Hofmann, Hajo Frerichs, Dalaver H Anjum, Tobias Reich, Ingo Lieberwirth, Martin Panthöfer, Wolfgang G Zeier, Wolfgang Tremel
The Magnéli phase V6O11 was synthesized in gram amounts from a powder mixture of V6O11/V7O13 and vanadium metal, using the spark plasma sintering (SPS) technique. Its structure was determined with synchrotron X-ray powder diffraction data from a phase-pure sample synthesized by conventional solid-state synthesis. A special feature of Magnéli-type oxides is a combination of crystallographic shear and intrinsic disorder that leads to relatively low lattice thermal conductivities. SPS prepared V6O11 has a relatively low thermal conductivity of κ = 2...
January 11, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29323391/growth-of-regular-nanometric-molecular-arrays-on-a-functional-2d-template-based-on-a-chemical-guest-host-approach
#11
Zhijing Feng, Gregor Kladnik, Giovanni Comelli, Carlo Dri, Albano Cossaro
A regular 2D array of crown molecules, which would spontaneously self-assemble into disordered molecular clusters, is obtained by exploiting a guest-host process, based on the chemical affinity between amino and carboxylic groups on a gold surface. First a carboxylic organic template is formed, which then serves as a host for amino-functionalized crown molecules. The amino-carboxylic interaction thereby drives the formation of a monolayer of guest molecules, regularly distributed at the nanometer scale, preventing their aggregation in unordered clusters observed on a bare gold surface...
January 11, 2018: Nanoscale
https://www.readbyqxmd.com/read/29323199/observation-of-carrier-localization-in-cubic-crystalline-ge2sb2te5-by-field-effect-measurement
#12
Hang Qian, Hao Tong, Ming-Ze He, Hong-Kai Ji, Ling-Jun Zhou, Ming Xu, Xiang-Shui Miao
The tunable disorder of vacancies upon annealing is an important character of crystalline phase-change material Ge2Sb2Te5 (GST). A variety of resistance states caused by different degrees of disorder can lead to the development of multilevel memory devices, which could bring a revolution to the memory industry by significantly increasing the storage density and inspiring the neuromorphic computing. This work focuses on the study of disorder-induced carrier localization which could result in multiple resistance levels of crystalline GST...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29322360/highly-conserved-arg-residue-of-erfnin-motif-of-pro-domain-is-important-for-ph-induced-zymogen-activation-process-in-cysteine-cathepsins-k-and-l
#13
Pulakesh Aich, Sampa Biswas
Pro-domain of a cysteine cathepsin contains a highly conserved Ex2Rx2Fx2Nx3Ix3N (ERFNIN) motif. The zymogen structure of cathepsins revealed that the Arg(R) residue of the motif is a central residue of a salt-bridge/H-bond network, stabilizing the scaffold of the pro-domain. Importance of the arginine is also demonstrated in studies where a single mutation (Arg → Trp) in human lysosomal cathepsin K (hCTSK) is linked to a bone-related genetic disorder "Pycnodysostosis". In the present study, we have characterized in vitro Arg → Trp mutant of hCTSK and the same mutant of hCTSL...
January 10, 2018: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29321443/a-new-arena-in-cardiac-surgery-pediatric-coronary-artery-bypass-surgery
#14
Soichiro Kitamura
Prior to the 1970s, pediatric coronary artery bypass surgery (PCABS) was seldomly performed due to the lack of compelling surgical indications. The advent of coronary sequelae secondary to Kawasaki disease (KD) and the occurrence of coronary artery complications due to newly developed procedures, such as the arterial switch operation and early repair for intrinsic congenital coronary malformations, necessitated the development of PCABS. Because children grow rapidly and their life expectancy is very long, with increasing exercise capability requirements, the strategy for PCABS should differ from that for bypass surgery in adults...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/29320696/using-a-fret-library-with-multiple-probe-pairs-to%C3%A2-drive-monte-carlo-simulations-of-%C3%AE-synuclein
#15
John J Ferrie, Conor M Haney, Jimin Yoon, Buyan Pan, Yi-Chih Lin, Zahra Fakhraai, Elizabeth Rhoades, Abhinav Nath, E James Petersson
We describe a strategy for experimentally-constraining computational simulations of intrinsically disordered proteins (IDPs), using α-synuclein, an IDP with a central role in Parkinson's disease pathology, as an example. Previously, data from single-molecule Förster Resonance Energy Transfer (FRET) experiments have been effectively utilized to generate experimentally constrained computational models of IDPs. However, the fluorophores required for single-molecule FRET experiments are not amenable to the study of short-range (<30 Å) interactions...
January 9, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29319897/application-of-a-physiologically-based-pharmacokinetic-model-for-the-prediction-of-bumetanide-plasma-and-brain-concentrations-in-the-neonate
#16
Maria D Donovan, Khaled Abduljalil, John F Cryan, Geraldine B Boylan, Brendan T Griffin
Bumetanide is a loop diuretic that is proposed to possess a beneficial effect on disorders of the central nervous system, including neonatal seizures. Therefore, prediction of unbound bumetanide concentrations in brain is relevant from a pharmacological prospective. A physiologically-based pharmacokinetic (PBPK) model was developed for the prediction of bumetanide disposition in plasma and brain in adult and pediatric populations. A compound file was built for bumetanide integrating physicochemical data and in vitro data...
January 10, 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29315236/understanding-the-role-of-intrinsic-disorder-of-viral-proteins-in-the-oncogenicity-of-different-types-of-hpv
#17
Elvira Regina Tamarozzi, Silvana Giuliatti
Intrinsic disorder is very important in the biological function of several proteins, and is directly linked to their foldability during interaction with their targets. There is a close relationship between the intrinsically disordered proteins and the process of carcinogenesis involving viral pathogens. Among these pathogens, we have highlighted the human papillomavirus (HPV) in this study. HPV is currently among the most common sexually transmitted infections, besides being the cause of several types of cancer...
January 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29314619/naringin-protects-pancreatic-%C3%AE-cells-against-oxidative-stress-induced-apoptosis-by-inhibiting-both-intrinsic-and-extrinsic-pathways-in-insulin-deficient-diabetic-mice
#18
Ye Jin Lim, Jung Ho Kim, Jeong Hoon Pan, Jae Kyeom Kim, Tae-Sik Park, Young Jun Kim, Jin Hyup Lee, Jun Ho Kim
SCOPE: Oxidative stress has been suggested to play a central role in the pathogenesis of diabetes, as well as other metabolic disorders. Naringin, a major flavanone glycoside in citrus species, has been shown to display strong antioxidant potential in in vitro and in vivo models of oxidative stress; however, the underlying protective mechanisms in diabetes are unclear. METHODS AND RESULTS: To study the protective effects and molecular mechanisms of naringin in preventing islet dysfunction and diabetes, we examined glucose homeostasis, β-cell apoptosis, and inflammatory response in insulin-deficient diabetic mice exposed to acute oxidative stress with streptozotocin (STZ)...
January 4, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29314492/the-binding-mode-of-a-repeat-like-tau-sequence-with-tubulin
#19
Harindranath Kadavath, Yunior Cabrales Fontela, Mariusz Jaremko, Lukasz Jaremko, Kerstin Overkamp, Jacek Biernat, Eckhard Mandelkow, Markus Zweckstetter
The microtubule-associated protein Tau promotes the polymerization of tubulin and modulates the function of microtubules. Because of the dynamic nature of the Tau/tubulin interaction, the structural basis of this complex has remained largely elusive. Using a combination of NMR methods optimized for ligand-receptor interactions and site-directed mutagenesis we demonstrate that the flanking domain downstream of the four microtubule-binding repeats of Tau binds competitively to a site on the α-tubulin surface...
January 3, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29314274/small-angle-x-ray-scattering-and-cross-linking-for-data-assisted-protein-structure-prediction-in-casp-12-with-prospects-for-improved-accuracy
#20
Tadeusz L Ogorzalek, Greg L Hura, Adam Belsom, Kathryn H Burnett, Andriy Kryshtafovych, John A Tainer, Juri Rappsilber, Susan E Tsutakawa, Krzysztof Fidelis
Experimental data offers empowering constraints for structure prediction. These constraints can be used to filter equivalently scored models or more powerfully within optimization functions toward prediction. In CASP12, Small Angle X-ray Scattering (SAXS) and Cross-Linking Mass Spectrometry (CLMS) data, measured on an exemplary set of novel fold targets, were provided to the CASP community of protein structure predictors. As HT, solution-based techniques, SAXS and CLMS can efficiently measure states of the full-length sequence in its native solution conformation and assembly...
January 4, 2018: Proteins
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