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Journal of Proteome Research

Luis Mendoza, Eric W Deutsch, Zhi Sun, David S Campbell, David D Shteynberg, Robert L Moritz
Bottom-up proteomics relies on the proteolytic or chemical cleavage of proteins into peptides, the identification of those peptides via mass spectrometry, and the mapping of the identified peptides back to the reference proteome to infer which possible proteins are identified. Reliable mapping of peptides to proteins still poses substantial challenges when considering similar proteins, protein families, splice isoforms, sequence variation, and possible residue mass modifications, combined with an imperfect and incomplete understanding of the proteome...
September 19, 2018: Journal of Proteome Research
Chiara Monti, Lydie Lane, Mauro Fasano, Tiziana Alberio
Due to the pivotal role of mitochondrial alterations in several diseases, the Human Proteome Organization (HUPO) has promoted in recent years an initiative to characterize the mitochondrial human proteome, the mitochondrial human proteome project (mt-HPP). Here, we generated an updated version of the functional mitochondrial human proteome network, made by nodes (mitochondrial proteins) and edges (gold binary interactions), using data retrieved from neXtProt, the reference database for HPP metrics. The principal new concept suggested was the consideration of mitochondria-associated proteins (first interactors), which may influence mitochondrial functions...
September 19, 2018: Journal of Proteome Research
S Ouml Ren Planckaert, Samuel Jourdan, Isolde M Francis, Benoit Deflandre, Sébastien Rigali, Bart Devreese
Streptomyces scabies is responsible for common scab disease on root and tuber vegetables. Production of its main phytotoxin thaxtomin A is triggered upon transport of cellulose byproducts cellotriose and cellobiose, which disable the repression of the thaxtomin biosynthesis activator gene txtR by the cellulose utilization regulator CebR. To assess the intracellular response under conditions where S. scabies develops a virulent behavior, we performed a comparative proteomic analysis of wild-type S. scabies 87-22 and its cebR null mutant (hyper-virulent phenotype) grown in the absence or presence of cellobiose...
September 19, 2018: Journal of Proteome Research
James R Anderson, Susama Chokesuwattanaskul, Marie M Phelan, Tim Jm Welting, Lu-Yun Lian, Mandy J Peffers, Helen L Wright
Despite osteoarthritis (OA) and rheumatoid arthritis (RA) being typically age-related, their underlying aetiologies are markedly different. We used 1H Nuclear Magnetic Resonance (NMR) spectroscopy to identify differences in metabolite profiles in low volumes of OA and RA synovial fluid (SF). SF was aspirated from knee joints of 10 OA and 14 RA patients. 100µL SF was analysed using a 700 MHz Avance IIIHD Bruker NMR spectrometer with a TCI cryoprobe. Spectra were analysed by Chenomx, Bruker TopSpin and AMIX software...
September 19, 2018: Journal of Proteome Research
Mengjie Yu, Shuilin Sun, Jiangqing Yu, Fen Du, Shouhua Zhang, Wenlong Yang, Juhua Xiao, Baogang Xie
To identify and screen serum biomarkers to determine pediatric patients with congenital heart diseases (PCH) from healthy control children (NC), a total of 614 clinically diagnosed subjects from three hospitals, including 491 PCH and 234 NC, were enrolled for nontargeted proton nuclear magnetic resonance spectroscopy (1 H NMR)-based and targeted ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS)-based metabolomics studies. Nineteen serum metabolites distinguishing PCH from NC were identified by 1 H NMR-based metabolomic analysis...
September 19, 2018: Journal of Proteome Research
Mario Navarrete, Julie Ho, Ravi C Dwivedi, Nora Choi, Peyman Ezzati, Victor Spicer, Rakesh C Arora, Claudio Rigatto, John A Wilkins
The processes involved in the initiation of acute kidney injury (AKI) following cardiopulmonary bypass (CPB) are thought to occur during the intraoperative period. Such a rapid development might indicate that some of the inductive events are not dependent on de novo protein synthesis, raising the possibility that changes in activities of pre-existing enzymes could contribute to the development of AKI. Activity-based protein profiling (ABPP) was used to compare the serine hydrolase enzyme activities present in the urines of CPB patients who subsequently developed AKI versus those who did not (non-AKI) during the intra- and immediate postoperative periods...
September 19, 2018: Journal of Proteome Research
Mingrui An, Jing Wu, Jianhui Zhu, David M Lubman
Exosomes are nanosized vesicles that are abundant in biological fluids. In recent years, exosomes have attracted increasing attention as their cargo may provide promising biomarkers for the early diagnosis of and therapy for many diseases, such as cancer. In addition to ultracentrifugation (UC), many alternative methods including size-exclusion chromatography (SEC) have been developed for isolating exosomes. It has been reported that the SEC method provided improved performance relative to the UC method in isolating exosomes from plasma, where the former contained less residual blood protein contamination...
September 19, 2018: Journal of Proteome Research
Elena Chekmeneva, Gonçalo Dos Santos Correia, María Gómez-Romero, Jeremiah Stamler, Queenie Chan, Paul Elliott, Jeremy K Nicholson, Elaine Holmes
The application of metabolic phenotyping to epidemiological studies involving thousands of biofluid samples presents a challenge for the selection of analytical platforms that meet the requirements of high-throughput precision analysis and cost-effectiveness. Here direct infusion-nanoelectrospray (DI-nESI) was compared with an ultra-performance liquid chromatography (UPLC)-high-resolution mass spectrometry (HRMS) method for metabolic profiling of an exemplary set of 132 human urine samples from a large epidemiological cohort...
September 19, 2018: Journal of Proteome Research
David Sehnal, Oliver C Grant
The representation of carbohydrates in 3D space using symbols is a powerful visualization method, but such representations are lacking in currently available visualization software. The work presented here allows researchers to display carbohydrate 3D structures as 3D-SNFG symbols using LiteMol from a web browser (e.g., ). Any PDB ID can be substituted at the end of the URL. Alternatively, the user may enter a PDB ID or upload a structure. LiteMol is available at https://v.litemol...
September 19, 2018: Journal of Proteome Research
Andrea F G Gargano, Jared B Shaw, Mowei Zhou, Christopher S Wilkins, Thomas L Fillmore, Ronald J Moore, Govert W Somsen, Ljiljana Paša-Tolić
Top-down proteomics is an emerging analytical strategy to characterize combinatorial protein post-translational modifications (PTMs). However, sample complexity and small mass differences between chemically closely related proteoforms often limit the resolution attainable by separations employing a single liquid chromatographic (LC) principle. In particular, for ultramodified proteins like histones, extensive and time-consuming fractionation is needed to achieve in-depth proteoform coverage. Herein, we present the first online nano-flow comprehensive two-dimensional liquid chromatography (nLC×LC) platform for top-down mass spectrometry analysis of histone proteoforms...
September 18, 2018: Journal of Proteome Research
Sebastian N W Hoernstein, Benjamin Fode, Gertrud Wiedemann, Daniel Lang, Holger Niederkrueger, Birgit Berg, Andreas Schaaf, Thomas Frischmuth, Andreas Schlosser, Eva L Decker, Ralf Reski
Host cell proteins are inevitable contaminants of biopharmaceuticals. Here, we performed detailed analyses of the host cell proteome of moss (Physcomitrella patens) bioreactor supernatants using mass spectrometry and subsequent bioinformatics analysis. Distinguishing between the apparent secretome and intracellular contaminants, a complex extracellular proteolytic network including subtilisin-like proteases, metallo-proteases and aspartic proteases was identified. Knockout of a subtilisin-like protease affected the overall extracellular proteolytic activity...
September 18, 2018: Journal of Proteome Research
Rongfeng Li, Huahua Yu, Yang Yue, Pengcheng Li
Jellyfish are a type of poisonous cnidarian invertebrate that secretes lethal venom for predation or defense. Human beings often become victims of jellyfish stings accidentally while swimming or fishing and suffer severe pain, itching, swelling, inflammation, shock and even death. Jellyfish venom is composed of various toxins, and the lethal toxin is the most toxic and hazardous component of the venom, which is responsible for deaths caused by jellyfish stings and envenomation. Our previous study revealed many toxins in jellyfish venom, including phospholipase A2, metalloproteinase and protease inhibitors...
September 18, 2018: Journal of Proteome Research
Vishak Raman, Uma K Aryal, Victoria Hedrick, Rodrigo Mohallem Ferreira, Jorge Luis Fuentes Lorenzo, Elena E Stashenko, Morris Levy, Maria M Levy, Ignacio G Camarillo
Triple-negative breast cancer is an aggressive subtype of breast cancer with low 5-year survival rates, high 3-year recurrence rates, and no known therapeutic targets. Recent studies have indicated that triple-negative breast cancers possess an altered metabolic state with higher rates of glycolysis, mitochondrial oxidative phosphorylation, and increased generation and utilization of tricarboxylic acid cycle intermediates. Here, we utilized label-free quantitative proteomics to gain insight into the anticancer mechanisms of a methanolic extract from the Central American plant Lippia origanoides on MDA-MB-231 triple-negative breast cancer cells...
September 18, 2018: Journal of Proteome Research
Leah V Schaffer, Jarred W Rensvold, Michael R Shortreed, Anthony J Cesnik, Adam Jochem, Mark Scalf, Brian L Frey, David J Pagliarini, Lloyd M Smith
The development of effective strategies for the comprehensive identification and quantification of proteoforms in complex systems is a critical challenge in proteomics. Proteoforms, the specific molecular forms in which proteins are present in biological systems, are the key effectors of biological function. Thus, knowledge of proteoform identities and abundances is essential to unraveling the mechanisms that underlie protein function. We recently reported a strategy that integrates conventional top-down mass spectrometry with intact-mass determinations for enhanced proteoform identifications and the elucidation of proteoform families and applied it to the analysis of yeast cell lysate...
September 18, 2018: Journal of Proteome Research
Upneet Kaur, He Meng, Fang Liu, Renze Ma, Ryenne N Ogburn, Julia H R Johnson, Michael C Fitzgerald, Lisa M Jones
Over the past decade a suite of new mass spectrometry-based proteomics methods has been developed that now enables the conformational properties of proteins and protein-ligand complexes to be studied in complex biological mixtures, from cell lysates to intact cells. Highlighted here are seven of the techniques in this new toolbox. These techniques include chemical cross-linking (XL-MS), hydroxyl radical footprinting (HRF), Drug Affinity Responsive Target Stability (DARTS), Limited Proteolysis (LiP), Pulse Proteolysis (PP), Stability of Proteins from Rates of Oxidation (SPROX) and Thermal Proteome Profiling (TPP)...
September 17, 2018: Journal of Proteome Research
Andy Lin, J Jeffry Howbert, William Stafford Noble
To achieve accurate assignment of peptide sequences to observed fragmentation spectra, a shotgun proteomics database search tool must make good use of the very high resolution information produced by state-of-the-art mass spectrometers. However, making use of this information while also ensuring that the search engine's scores are well calibrated -- i.e., that the score assigned to one spectrum can be meaningfully compared to the score assigned to a different spectrum -- has proven to be challenging. Here, we describe a database search score function, the "residue evidence" (res-ev) score, that achieves both of these goals simultaneously...
September 17, 2018: Journal of Proteome Research
Jatin Shrinet, Priyanshu Srivastava, Ankit Kumar, Sunil Kumar Dubey, Pahala Dickwellage Nadeera Nilupamali Sirisena, Pratibha Srivastava, Sujatha Sunil
Chikungunya virus (CHIKV) and dengue virus (DENV) are important arboviruses transmitted by Aedes mosquitoes. These viruses are known to coexist within the same vector and coinfect the same host. Although information is available on the mechanism of replication of CHIKV and DENV when present independently in a vector, reports are lacking on the dynamics of virus-vector interactions when these viruses coexist in a mosquito. The current study attempts to understand the perturbations in the proteome of Aedes mosquitoes when infected with CHIKV and DENV either independently or together...
September 17, 2018: Journal of Proteome Research
Feng-Jin Shao, Yi-Tian Ying, Xun Tan, Qiao-Yan Zhang, Wen-Ting Liao
Pulmonary arterial hypertension (PAH) is the major cause of death in fast growing meat-type chickens (broiler chickens). At present, the underlying mechanisms that give rise to PAH are not fully understood. To identify the metabonomics profiles characterizing the process, we conducted a comprehensive gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of lung tissues from PAH broilers and age-matched controls. PAH was induced by excess salt in drinking water. Medial hypertrophy of pulmonary arteries was present in PAH birds as compared with controls...
September 17, 2018: Journal of Proteome Research
Thibault Robin, Amos Bairoch, Markus Müller, Frédérique Lisacek, Lydie Lane
The practice of data sharing in the proteomics field took off and quickly spread in recent years as a result of collective effort. Nowadays, most journal editors mandate the submission of the original raw mass spectra to one of the databases of the ProteomeXchange consortium. With the exception of large institutional initiatives such as PeptideAtlas or the GPMDB, few new studies are however based on the reanalysis of mass spectrometry data. A wealth of information is thus left unexploited in public databases and repositories...
September 17, 2018: Journal of Proteome Research
Christian D Kelstrup, Konstantin Aizikov, Tanveer S Batth, Arne Kreutzman, Dmitry Grinfeld, Oliver Lange, Daniel Mourad, Alexander A Makarov, Jesper V Olsen
A popular method for peptide quantification relies on isobaric labeling such as tandem mass tags (TMT) which enables multiplexed proteome analyses. Quantification is achieved by reporter ions generated by fragmentation in a tandem mass spectrometer. However, with higher degrees of multiplexing, the smaller mass differences between the reporter ions increase the mass resolving power requirements. This contrasts with faster peptide sequencing capabilities enabled by lowered mass resolution on Orbitrap instruments...
September 16, 2018: Journal of Proteome Research
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