Read by QxMD icon Read


Hasup Lee, Minkyung Baek, Gyu Rie Lee, Sangwoo Park, Chaok Seok
Many proteins function as homo- or hetero-oligomers; therefore, attempts to understand and regulate protein functions require knowledge of protein oligomer structures. The number of available experimental protein structures is increasing, and oligomer structures can be predicted using the experimental structures of related proteins as templates. However, template-based models may have errors due to sequence differences between the target and template proteins, which can lead to functional differences. Such structural differences may be predicted by loop modeling of local regions or refinement of the overall structure...
October 22, 2016: Proteins
David J Koss, Glynn Jones, Anna Cranston, Heidi Gardner, Nicholas M Kanaan, Bettina Platt
Post-mortem investigations of human Alzheimer's disease (AD) have largely failed to provide unequivocal evidence in support of the original amyloid cascade hypothesis, which postulated deposition of β-amyloid (Aβ) aggregates to be the cause of a demented state as well as inductive to tau neurofibrillary tangles (NFTs). Conflicting evidence suggests, however, that Aβ plaques and NFTs, albeit to a lesser extent, are present in a substantial subset of non-demented individuals. Hence, a range of soluble tau and Aβ species has more recently been implicated as the disease-relevant toxic entities...
October 21, 2016: Acta Neuropathologica
Jamie L Burgess, R Alan Burgess, Yalemi Morales, Jenna M Bouvang, Sean J Johnson, Nicholas E Dickenson
Like many Gram-negative pathogens, Shigella rely on a complex type three secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high-resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific sidechain contributions from adjacent protomers within the complex...
October 21, 2016: Journal of Biological Chemistry
Maria Gregori, Mark Taylor, Elisa Salvati, Francesca Re, Simona Mancini, Claudia Balducci, Gianluigi Forloni, Vanessa Zambelli, Silvia Sesana, Maria Michael, Christos Michail, Claire Tinker-Mill, Oleg Kolosov, Michael Scherer, Stephen Harris, Nigel J Fullwood, Massimo Masserini, David Allsop
Aggregation of Amyloid-β peptide (Aβ) is a key event in the pathogenesis of Alzheimer's disease (AD). We investigated the effects of nanoliposomes decorated with the retro-inverso peptide RI-OR2-TAT (Ac-rGffvlkGrrrrqrrkkrGy-NH2) on the aggregation and toxicity of Aβ. Remarkably low concentrations of these peptide inhibitor nanoparticles (PINPs) were required to inhibit the formation of Aβ oligomers and fibrils in vitro, with 50% inhibition occurring at a molar ratio of ~1:2000 of liposome-bound RI-OR2-TAT to Aβ...
October 18, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Shuai Gao, Man Pan, Yong Zheng, Yichao Huang, Qingyun Zheng, Demeng Sun, Lining Lu, Xiaodan Tan, Xianglong Tan, Huan Lan, Jiaxing Wang, Tian Wang, Jiawei Wang, Lei Liu
Racemic or quasi-racemic crystallography recently emerges as a useful technology for solution of the crystal structures of biomacromolecules. It remains unclear to what extent the biomacromolecules of opposite handedness can differ from each other in racemic or quasi-racemic crystallography. Here we report a finding that monomeric d-ubiquitin (Ub) has propensity to cocrystallize with different dimers, trimers, and even a tetramer of l-Ub. In these cocrystals the unconnected monomeric d-Ubs can self-assemble to form pseudomirror images of different oligomers of l-Ub...
October 21, 2016: Journal of the American Chemical Society
Natarajan Suganthy, Dicson Sheeja Malar, Kasi Pandima Devi
OBJECTIVE: Amyloid hypothesis states that endogenous β-amyloid peptides (Aβ), especially its aggregated oligomers and fibrils are the key pathogenic factors leading to Alzheimer's disease (AD). Therefore, inhibition of Aβ fibrillation rather than blocking its production is considered promising therapeutic intervention. Hence, the present study was carried out to assess the effect of methanolic leaf extract of R. mucronata (MERM) and its bioactive compound catechin on in vitro fibrillation of Aβ (25-35)...
October 21, 2016: Neurological Research
Himanshu Chaudhary, Aditya Iyer, Vinod Subramaniam, Mireille M A E Claessens
Phospholipid vesicles are commonly used to get insight into the mechanism by which oligomers of amyloidogenic proteins damage membranes. Oligomers of the protein α-synuclein (αS) are thought to create pores in phospholipid vesicles containing a high amount of anionic phospholipids but fail to damage vesicle membranes at lower surface charge densities. The current understanding of how αS oligomers damage membranes is thus incomplete. This incomplete understanding may, in part, result from the choice of model membrane systems...
October 21, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Floriana Foarta, Clark R Landis
A novel strategy, free of coupling reagents and protection/deprotection steps, for the synthesis of oligo(2-hydroxyacid)s containing up to four monomer units with atom economy, sequence specificity, and control of stereocenter configuration is described. The strategy comprises an iterative application of the sequence asymmetric hydroformylation / oxidation / alkyne hydroacyloxylation that features catalytic, atom-economical C-C and C-O bond forming reactions. Asymmetric hydroformylation with Rh-bisdiazaphospholane catalyst introduces each stereocenter with high enantio- (ca...
October 21, 2016: Journal of Organic Chemistry
Cinzia Guzzi, Laura Colombo, Ada De Luigi, Mario Salmona, Francesco Nicotra, Cristina Airoldi
Combining NMR spectroscopy, transmission electron microscopy, biochemical and in vitro toxicity assays, we characterized the effect of flavonoid glycosylation, a chemical modification very frequent in Nature, on their ability to recognise and bind Aβ1-42 oligomers, preventing their aggregation and their neurotoxicity. Our data allow the elucidation of their structure activity relationships, showing that glycosylation has a modest impact on flavonoid affinity for Aβ oligomers but, at the same time, increases both solubility and chemical stability, thus promoting their beneficial properties against Alzheimer's diseases (AD)...
October 21, 2016: Chemistry, An Asian Journal
Przemyslaw Jurczak, Patrick Groves, Aneta Szymanska, Sylwia Rodziewicz-Motowidlo
Human cystatin C (hCC) is a small protein belonging to the cystatin family of papain-like cysteine proteinase inhibitors. We review the recent literature concerning structural aspects of hCC related to disease. We focus on the mechanisms of hCC dimerization, oligomerization and amyloid formation. Amyloid formation is associated with a number of neurodegenerative diseases that affect the independence and quality of life of aging populations. hCC is one of the second wave proteins that have been found to undergo amyloidosis associated with disease...
October 19, 2016: FEBS Letters
Neha Kumari, Rajesh Kumar, Vandana Mishra, Savita Yadav
CC-NBS-LRR (CNL) plant proteins are related with highly conserved family of disease resistance protein distinguished by a coiled-coil domain, which plays an important role in innate immunity. The present study reports the purification and identification of CNL like protein fragment (CNL-LPF) by two step chromatography and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF/MS), respectively. Furthermore, current study also illustrated the development of polyclonal antibody against purified CNL-LPF, which was used for immunolocalization of CNL-LPF in cytoplasm of cotyledon, using Fluorescence microscopy and Transmission electron microscopy...
October 20, 2016: Protein Journal
Anna V Glyakina, Nikolai K Balabaev, Oxana V Galzitskaya
The amyloidogenic peptide VDSWNVLVAG from Bgl2p-glucantransferase of Saccharomyces cerevisiae cell wall and its modifying analog VESWNVLVAG were taken for the construction of four types of bilayers which differ by orientation of the peptides in the layers and of the layers relative to each other. These bilayers were used as starting models for the molecular dynamics (MD) at three charge states (neutral, pH3, and pH5). The changes of the fraction of secondary structure during 1 ns simulations were received for 96 MD trajectories...
December 2016: Data in Brief
J T Oberlerchner, P Vejdovszky, T Zweckmair, A Kindler, S Koch, T Rosenau, A Potthast
Degraded celluloses are becoming increasingly important as part of product streams coming from various biorefinery scenarios. Analysis of the molar mass distribution of such fractions is a challenge, since neither established methods for mono- or disaccharides nor common methods for polysaccharide characterization cover the intermediate oligomer range appropriately. Size exclusion chromatography (SEC) with multi-angle laser light scattering (MALLS), the standard approach for celluloses, suffers from decreased scattering intensities in the lower-molar mass range...
October 8, 2016: Journal of Chromatography. A
Robert F Gahl, Pallavi Dwivedi, Nico Tjandra
The most critical step in the initiation of apoptosis is the activation of the Bcl-2 family of proteins to oligomerize and permeabilize the outer-mitochondrial membrane (OMM). As this step results in the irreversible release of factors that enhance cellular degradation, it is the point of no return in programmed cell death and would be an ideal therapeutic target. However, the arrangement of the Bcl-2 proteins in the OMM during permeabilization still remains unknown. It is also unclear whether the Bcl-2 protein, Bid, directly participates in the formation of the oligomers in live cells, even though it is cleaved and translocates to the OMM at the initiation of apoptosis...
October 20, 2016: Cell Death & Disease
John A Karas, Nitin A Patil, Julien Tailhades, Marc-Antoine Sani, Denis B Scanlon, Briony E Forbes, James Gardiner, Frances Separovic, John D Wade, Mohammed Akhter Hossain
Despite recent advances in the treatment of diabetes mellitus, storage of insulin formulations at 4 °C is still necessary to minimize chemical degradation. This is problematic in tropical regions where reliable refrigeration is not ubiquitous. Some degradation byproducts are caused by disulfide shuffling of cystine that leads to covalently bonded oligomers. Consequently we examined the utility of the non-reducible cystine isostere, cystathionine, within the A-chain. Reported herein is an efficient method for forming this mimic using simple monomeric building blocks...
October 20, 2016: Angewandte Chemie
Martin Jopcik, Jana Moravcikova, Ildiko Matusikova, Miroslav Bauer, Miroslav Rajninec, Jana Libantova
Chitinase gene from the carnivorous plant, Drosera rotundifolia , was cloned and functionally characterised. Plant chitinases are believed to play an important role in the developmental and physiological processes and in responses to biotic and abiotic stress. In addition, there is growing evidence that carnivorous plants can use them to digest insect prey. In this study, a full-length genomic clone consisting of the 1665-bp chitinase gene (gDrChit) and adjacent promoter region of the 698 bp in length were isolated from Drosera rotundifolia L...
October 19, 2016: Planta
Moran Frenkel-Pinter, Sharon Tal, Roni Scherzer-Attali, Malak Abu-Hussien, Idan Alyagor, Tal Eisenbaum, Ehud Gazit, Daniel Segal
Alzheimer's disease (AD) is the most abundant tauopathy and is characterized by Aβ-derived plaques and tau-derived tangles, resulting from the unfolding of the corresponding monomeric subunits into ordered β-sheet oligomers and fibrils. Intervening in the toxic aggregation process is a promising therapeutic approach, but, to date, a disease-modifying therapy is neither available for AD nor for other tauopathies. Along these lines, we have previously demonstrated that a small naphthoquinone-tryptophan hybrid, termed NQTrp, is an effective modulator of tauopathy in vitro and in vivo...
October 20, 2016: Neuro-degenerative Diseases
Qin Qiao, Ruxi Qi, Guanghong Wei, Xuhui Huang
Amyloid deposits of human islet amyloid polypeptide (hIAPP) are identified in 95% of type II diabetes patients. The oligomers during the early stage of hIAPP aggregation are believed to be more cytotoxic than the mature fibrils. However, the structural details during the initial stage of hIAPP aggregation are still under debate experimentally. To understand its initial nucleation mechanism, we investigate the thermodynamics and kinetics of hIAPP(11-25) dimerization, which is the first manifestation of the interplay between intra- and inter-molecular interactions, via the construction of Markov state models from extensive molecular dynamics simulations...
October 19, 2016: Physical Chemistry Chemical Physics: PCCP
Ying Wei, Jun Lu, Tong Lu, Feihong Meng, Jia Xu, Li Wang, Yang Li, Liping Wang, Fei Li
Prefibrillar amyloid aggregates of proteins are known as cytotoxic species and a common pathogenic factor for many degenerative diseases. The mechanism underlying the formation and cytotoxicity of prefibrillar aggregates is believed to be independent of the actual nature of the amyloid protein. In this study, we monitored the formation of the peptide oligomers and examined the disruptive effects of the oligomers on liposomes using the human islet amyloid polypeptide fragment hIAPP18-27 as a model peptide. We observed various morphologies of oligomers formed at different aggregation stages that precede the formation of mature amyloid fibrils...
October 19, 2016: Physical Chemistry Chemical Physics: PCCP
Lixin Xia, Jing Wang, Caiqing Ma, Shiwei Wu, Peng Song
The vibrational spectra have been investigated for revealing the comprehensive structure of diferrocenyl-oligothienylene-vinylene complex, stimulated by the excellent experimental reports [group of Casado J. Am. Chem. Soc. 2012, 134, 12, 5675]. The IR and Raman spectra were simulated. It is found that the change of charge distribution and bond length are associated with the variation in the frequencies of specific vibration in infrared spectra for the neutral and radical oxidation states. The theoretical simulation of charge difference density indicate that charge transfer mechanism for neutral and dication states are significant different...
October 19, 2016: Scientific Reports
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"