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Intrinsically disordered

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https://www.readbyqxmd.com/read/28109332/structural-characteristics-of-%C3%AE-synuclein-oligomers
#1
N Cremades, S W Chen, C M Dobson
Oligomeric forms of amyloid aggregates have been detected in the brains and tissues of patients suffering from neurodegenerative disorders such as Parkinson's disease, and it is widely thought that such species are key pathogenic agents in the development and spreading of the disease; however, the study of these species has been proven to be extremely challenging, primarily as a result of their intrinsically transient nature and high levels of heterogeneity. Identifying the structural nature and the details of the mechanisms of formation and interconversion of individual oligomeric species, particularly those with high toxicity, is of fundamental importance not only for understanding the mechanisms of protein misfolding and amyloid aggregation but also for the identification of diagnostic and therapeutic targets...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28109327/effects-of-intrinsic-and-extrinsic-factors-on-aggregation-of-physiologically-important-intrinsically-disordered-proteins
#2
L Breydo, J M Redington, V N Uversky
Misfolding and aggregation of proteins and peptides play an important role in a number of diseases as well as in many physiological processes. Many of the proteins that misfold and aggregate in vivo are intrinsically disordered. Protein aggregation is a complex multistep process, and aggregates can significantly differ in morphology, structure, stability, cytotoxicity, and self-propagation ability. The aggregation process is influenced by both intrinsic (e.g., mutations and expression levels) and extrinsic (e...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28109185/folding-of-intrinsically-disordered-plant-lea-proteins-is-driven-by-glycerol-induced-crowding-and-the-presence-of-membranes
#3
Anne Bremer, Martin Wolff, Anja Thalhammer, Dirk K Hincha
Late embryogenesis abundant (LEA) proteins are related to cellular dehydration tolerance. Most LEA proteins are predicted to have no stable secondary structure in solution, i.e. to be intrinsically disordered proteins (IDPs), but they may acquire α-helical structure upon drying. In the model plant Arabidopsis thaliana the LEA proteins COR15A and COR15B are highly induced upon cold treatment and are necessary for the plants to attain full freezing tolerance. Freezing leads to increased intracellular crowding due to dehydration by extracellular ice crystals...
January 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28108951/physiological-links-of-circadian-clock-and-biological-clock-of-aging
#4
REVIEW
Fang Liu, Hung-Chun Chang
Circadian rhythms orchestrate biochemical and physiological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold self-sustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photoperiod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles...
January 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28108647/effects-of-early-life-exposure-to-thip-on-brainstem-neuronal-excitability-in-the-mecp2-null-mouse-model-of-rett-syndrome-before-and-after-drug-withdrawal
#5
Weiwei Zhong, Christopher M Johnson, Ningren Cui, Max F Oginsky, Yang Wu, Chun Jiang
Rett syndrome (RTT) is mostly caused by mutations of the X-linked MECP2 gene. Although the causal neuronal mechanisms are still unclear, accumulating experimental evidence obtained from Mecp2(-/Y) mice suggests that imbalanced excitation/inhibition in central neurons plays a major role. Several approaches may help to rebalance the excitation/inhibition, including agonists of GABAA receptors (GABAAR). Indeed, our previous studies have shown that early-life exposure of Mecp2-null mice to the extrasynaptic GABAAR agonist THIP alleviates several RTT-like symptoms including breathing disorders, motor dysfunction, social behaviors, and lifespan...
January 2017: Physiological Reports
https://www.readbyqxmd.com/read/28104899/amino-acid-based-material-for-the-complementary-therapy-of-decubitus-ulcers
#6
Frederico Nogueira, Isabel C Gouveia
Chronic wounds, pressure sores, lesions and infections of microbial origin in bedridden, paralyzed or malnutrition patients remain the object of study of many researchers. There are several intrinsic and extrinsic factors involved in the development of these disorders, which are related to the patient's immune system, making it unable to respond effectively to the treatment of the wound. These factors can be properly controlled, giving particular importance to the ethiology and stage of the wound, as well as the time periods corresponding to the replacement of the dressings...
January 20, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28104628/mobidb-lite-fast-and-highly-specific-consensus-prediction-of-intrinsic-disorder-in-proteins
#7
Marco Necci, Damiano Piovesan, Zsuzsanna Dosztányi, Silvio C E Tosatto
MOTIVATION: Intrinsic disorder (ID) is established as an important feature of protein sequences. Its use in proteome annotation is however hampered by the availability of many methods with similar performance at the single residue level, which have mostly not been optimized to predict long ID regions of size comparable to domains. Here, we have focused on providing a single consensus-based prediction, MobiDB-lite, optimized for highly specific (i.e. few false positive) predictions of long disorder...
January 18, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28103527/distinct-cortico-striatal-connections-with-subthalamic-nucleus-underlie-facets-of-compulsivity
#8
Laurel S Morris, Kwangyeol Baek, Valerie Voon
The capacity to flexibly respond to contextual changes is crucial to adapting to a dynamic environment. Compulsivity, or behavioural inflexibility, consists of heterogeneous subtypes with overlapping yet discrete neural substrates. The subthalamic nucleus (STN) mediates the switch from automatic to controlled processing to slow, break or stop behaviour when necessary. Rodent STN lesions or inactivation are linked with perseveration or repetitive, compulsive responding. However, there are few studies examining the role of latent STN-centric neural networks and compulsive behaviour in healthy individuals...
December 29, 2016: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/28101529/cortico-cortical-connections-of-primary-sensory-areas-and-associated-symptoms-in-migraine
#9
Duncan J Hodkinson, Rosanna Veggeberg, Aaron Kucyi, Koene R A van Dijk, Sophie L Wilcox, Steven J Scrivani, Rami Burstein, Lino Becerra, David Borsook
Migraine is a recurring, episodic neurological disorder characterized by headache, nausea, vomiting, and sensory disturbances. These events are thought to arise from the activation and sensitization of neurons along the trigemino-vascular pathway. From animal studies, it is known that thalamocortical projections play an important role in the transmission of nociceptive signals from the meninges to the cortex. However, little is currently known about the potential involvement of cortico-cortical feedback projections from higher-order multisensory areas and/or feedforward projections from principle primary sensory areas or subcortical structures...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28100789/complex-evolutionary-history-of-the-mammalian-histone-h1-1-h1-5-gene-family
#10
Inma Ponte, Devani Romero, Daniel Yero, Pedro Suau, Alicia Roque
H1 is involved in chromatin higher-order structure and gene regulation. H1 has a tripartite structure. The central domain is stably folded in solution, while the N- and C-terminal domains are intrinsically disordered. The terminal domains are encoded by DNA of low sequence complexity, and are thus prone to short insertions/deletions (indels). We have examined the evolution of the H1.1-H1.5 gene family from 27 mammalian species. Multiple sequence alignment has revealed a strong preferential conservation of the number and position of basic residues among paralogs, suggesting that overall H1 basicity is under a strong purifying selection...
January 18, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28100050/charge-carrier-hopping-dynamics-in-homogeneously-broadened-pbs-quantum-dot-solids
#11
Rachel H Gilmore, Elizabeth M Y Lee, Mark C Weidman, Adam P Willard, William A Tisdale
Energetic disorder in quantum dot solids adversely impacts charge carrier transport in quantum dot solar cells and electronic devices. Here, we use ultrafast transient absorption spectroscopy to show that homogeneously broadened PbS quantum dot arrays (σhom(2):σinh(2)>19:1, σinh/kBT<0.4) can be realized if quantum dot batches are sufficiently monodisperse (δ ≲ 3.3%). Homogeneous linewidth is found to be an inverse function of quantum dot size, monotonically increasing from ~25 meV for the largest quantum dots (5...
January 19, 2017: Nano Letters
https://www.readbyqxmd.com/read/28098335/not-an-exception-to-the-rule-the-functional-significance-of-intrinsically-disordered-protein-regions-in-enzymes
#12
Shelly DeForte, Vladimir N Uversky
Intrinsically disordered protein regions (IDPRs) are remarkably common and have unique and important biological functions. Enzymes have long been considered an exception to the rule of protein intrinsic disorder due to the structural requirements for catalysis. Although functionally significant IDPRs have been described in several enzymes, there has been no study quantifying the extent of this phenomenon. We have conducted a multilevel computational analysis of missing regions in X-ray crystal structures in the PDB and predicted disorder in 66 representative proteomes...
January 18, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28097742/differential-dehydration-effects-on-globular-proteins-and-intrinsically-disordered-proteins-during-film-formation
#13
Juliana Sakamoto Yoneda, Andew J Miles, Ana Paula Ulian de Araujo, B A Wallace
Globular proteins composed of different secondary structures and fold types were examined by synchrotron radiation circular dichroism spectroscopy to determine the effects of dehydration on their secondary structures. They exhibited only minor changes upon removal of bulk water during film formation, contrary to previously reported studies of proteins dehydrated by lyophilisation (where substantial loss of helical structure and gain in sheet structure was detected). This near lack of conformational change observed for globular proteins contrasts with intrinsically disordered proteins (IDPs) dried in the same manner: the IDPs, which have almost completely unordered structures in solution, exhibited increased amounts of regular (mostly helical) secondary structures when dehydrated, suggesting formation of new intra-protein hydrogen bonds replacing solvent-protein hydrogen bonds, in a process which may mimic interactions that occur when IDPs bind to partner molecules...
January 18, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28095698/evaluation-of-the-coupled-two-dimensional-main-chain-torsional-potential-in-modeling-intrinsically-disordered-proteins
#14
Ya Gao, Chaomin Zhang, John Z H Zhang, Ye Mei
Intrinsically Disordered Proteins (IDPs) carry out crucial biological functions in essential biological processes of life. Due to the highly dynamic and conformationally heterogeneous nature of the disordered states of IDPs, molecular dynamics simulations are becoming an indispensable tool for the investigation of the conformational ensembles and dynamic properties of IDPs. Nevertheless, there is still no consensus on the most reliable force field in molecular dynamics simulations for IDPs hitherto. In this work, a recently proposed AMBER99SB2D force field is evaluated in modeling some disordered polypeptides and proteins by checking its ability in reproducing NMR experimental data...
January 18, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28094514/structural-model-of-the-tubular-assembly-of-the-rous-sarcoma-virus-capsid-protein
#15
Jaekyun Jeon, Xin Qiao, Ivan Hung, Alok K Mitra, Ambroise Desfosses, Daniel Huang, Peter L Gor'kov, Rebecca C Craven, Richard L Kingston, Zhehong Gan, Fangqiang Zhu, Bo Chen
The orthoretroviral capsid protein (CA) assembles into polymorphic capsids, whose architecture, assembly and stability are still being investigated. The N-terminal and C-terminal domains of CA (NTD and CTD, respectively) engage in both homotypic and heterotypic interactions to create the capsid. Hexameric turrets formed by the NTD decorate the majority of the capsid surface. We report nearly-complete solid-state NMR (ssNMR) resonance assignments of Rous sarcoma virus (RSV) CA, assembled into hexamer tubes that mimic the authentic capsid...
January 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28094373/conformational-dynamics-and-self-association-of-intrinsically-disordered-huntingtin-exon-1-in-cells
#16
Steffen Büning, Abhishek Sharma, Shivang Vachharajani, Estella Newcombe, Angelique Ormsby, Mimi Gao, David Gnutt, Tobias Vöpel, Danny M Hatters, Simon Ebbinghaus
Huntington's disease is caused by a CAG trinucleotide expansion mutation in the Huntingtin gene that leads to an artificially long polyglutamine sequence in the Huntingtin protein. A key feature of the disease is the intracellular aggregation of the Huntingtin exon 1 protein (Httex1) into micrometer sized inclusion bodies. The aggregation process of Httex1 has been extensively studied in vitro, however, the crucial early events of nucleation and aggregation in the cell remain elusive. Here, we studied the conformational dynamics and self-association of Httex1 by in-cell experiments using laser-induced temperature jumps and analytical ultracentrifugation...
January 17, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28094245/external-magnetic-field-dependent-shift-of-superparamagnetic-blocking-temperature-due-to-core-surface-disordered-spin-interactions
#17
Kwan Lee, Jung-Tak Jang, Hiroshi Nakano, Shigeki Nakagawa, Sun Ha Paek, Seongtae Bae
Although the blocking temperature of superparamagnetic nanoparticles (SPNPs) is crucial for various spintronics and biomedical applications, the precise determination of the blocking temperature is still not clear. Here, we present 'intrinsic' and 'extrinsic' characteristics of the blocking temperature in SPNP systems. In zero-field-cooled/field-cooled (ZFC-FC) curves, there was no shift of 'intrinsic blocking temperature' at different applied external (excitation) magnetic fields. However, 'extrinsic blocking temperature' shift is clearly dependent on the external (excitation) magnetic field...
February 17, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28092832/sampling-conformational-space-of-intrinsically-disordered-proteins-in-explicit-solvent-comparison-between-well-tempered-ensemble-approach-and-solute-tempering-method
#18
Mengzhi Han, Ji Xu, Ying Ren
Intrinsically disordered proteins (IDPs) are a class of proteins that expected to be largely unstructured under physiological conditions. Due to their heterogeneous nature, experimental characterization of IDP is challenging. Temperature replica exchange molecular dynamics (T-REMD) is a widely used enhanced sampling method to probe structural characteristics of these proteins. However, its application has been hindered due to its tremendous computational cost, especially when simulating large systems in explicit solvent...
December 28, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28092089/time-dependent-lactate-production-and-amino-acid-utilization-in-cultured-astrocytes-under-high-glucose-exposure
#19
Dan Wang, Liangcai Zhao, Hong Zheng, Minjian Dong, Linlin Pan, Xi Zhang, Huajie Zhang, Hongchang Gao
Accumulating investigations have focused on the severity of central nervous system (CNS) complications in diabetic patients. The effects of the high glucose (HG) probably attribute to the metabolic disturbances in CNS. Astrocytes, with powerful ability of metabolic regulation, play crucial roles in physiological and pathological processes in CNS. Hence, an in-depth analysis as to metabolic alterations of astrocytes exposure to HG would facilitate to explore the underlying pathogenesis. In this study, the (1)H NMR-based metabonomic approach was performed to characterize the metabolic variations of intracellular metabolites and corresponding culture media in a time-dependent manner...
January 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28091762/good-jobs-good-pay-better-health-the-effects-of-job-quality-on-health-among-older-european-workers
#20
Golo Henseke
Using data from the Survey of Health, Ageing and Retirement in Europe, this study presents new evidence on the effects of job quality on the occurrence of severe acute conditions, the level of cardiovascular risk factors, musculoskeletal disorders, mental health, functional disabilities and self-assessed health among workers aged 50+. By combining intrinsic job quality with job insecurity and pay the study maps out multiple potential pathways through which work may affect health and well-being. Levering longitudinal data and external information on early retirement ages allows for accounting of unobserved heterogeneity, selection bias and reverse causality...
January 13, 2017: European Journal of Health Economics: HEPAC: Health Economics in Prevention and Care
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