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https://www.readbyqxmd.com/read/28757614/high-level-intrinsic-disorder-explains-the-universality-of-clip-binding-to-diverse-mhc-class-ii-variants
#1
Vladimir N Uversky, Yaping N Tu, Onyekachi Nwogu, Shanitra N Butler, Michael Ramsamooj, George Blanck
No abstract text is available yet for this article.
July 31, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28746777/functionality-of-intrinsic-disorder-in-tumor-necrosis-factor-%C3%AE-and-its-receptors
#2
Vladimir N Uversky, Nawal Abd El-Baky, Esmail M El-Fakharany, Amira Sabry, Ehab H Mattar, Alexey V Uversky, Elrashdy M Redwan
Tumor necrosis factor-α (TNF-α) is a pleiotropic inflammatory cytokine that exerts potent cytotoxic effects on solid tumor cells, while not affecting their normal counterparts. It is also known that TNF-α exerts many of its biological functions via interaction with specific receptors. To understand the potential roles of intrinsic disorder in the functioning of this important cytokine, we explored the peculiarities of intrinsic disorder distribution in human TNF-α and its homologues from various species, ranging from zebrafish to chimpanzee...
July 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28729736/the-relationship-between-folding-and-activity-in-ureg-an-intrinsically-disordered-enzyme
#3
Marta Palombo, Alessio Bonucci, Emilien Etienne, Stefano Ciurli, Vladimir N Uversky, Bruno Guigliarelli, Valérie Belle, Elisabetta Mileo, Barbara Zambelli
A growing body of literature on intrinsically disordered proteins (IDPs) led scientists to rethink the structure-function paradigm of protein folding. Enzymes are often considered an exception to the rule of intrinsic disorder (ID), believed to require a unique structure for catalysis. However, recent studies revealed the presence of disorder in several functional native enzymes. In the present work, we address the importance of dynamics for catalysis, by investigating the relationship between folding and activity in Sporosarcina pasteurii UreG (SpUreG), a P-loop GTPase and the first discovered native ID enzyme, involved in the maturation of the nickel-containing urease...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28726924/peculiarities-of-thermal-denaturation-of-ompf-porin-from-yersinia-ruckeri
#4
Olga D Novikova, Dmitry K Chistyulin, Valentina A Khomenko, Evgeny V Sidorin, Natalya Yu Kim, Nina M Sanina, Olga Yu Portnyagina, Tamara F Solov'eva, Vladimir N Uversky, Valery L Shnyrov
Irreversible denaturation of membrane proteins in detergent solutions is similar to unfolding of water-soluble multidomain proteins and represents a complex, multistage process. Pore-forming proteins of Gram-negative bacteria are heat-modifiable proteins, i.e., proteins altering their molecular forms (trimers or monomers), and accordingly, their electrophoretic mobilities depending upon denaturation conditions. There are still some contradictory data on the peculiarities of the conformational changes in the porin structure with temperature...
July 20, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28692085/functional-roles-of-intrinsic-disorder-in-crispr-associated-protein-cas9
#5
Zhihua Du, Vladimir N Uversky
Protein intrinsic disorder is an important characteristic commonly detected in multifunctional or RNA- and DNA-binding proteins. Due to their high conformational flexibility and solvent accessibility, intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) execute diverse functions including interaction with multiple partners, and are frequently subjected to various post-translational modifications. Recent studies on the components comprising the CRISPR (clustered regularly interspaced short palindromic repeats) system have elucidated the crystal structure of Cas9 proteins and the mechanism by which the Cas9-sgRNA complex recognizes and cleaves its target DNA...
July 10, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28654636/human-cyclophilin-40-unravels-neurotoxic-amyloids
#6
Jeremy D Baker, Lindsey B Shelton, Dali Zheng, Filippo Favretto, Bryce A Nordhues, April Darling, Leia E Sullivan, Zheying Sun, Parth K Solanki, Mackenzie D Martin, Amirthaa Suntharalingam, Jonathan J Sabbagh, Stefan Becker, Eckhard Mandelkow, Vladimir N Uversky, Markus Zweckstetter, Chad A Dickey, John Koren, Laura J Blair
The accumulation of amyloidogenic proteins is a pathological hallmark of neurodegenerative disorders. The aberrant accumulation of the microtubule associating protein tau (MAPT, tau) into toxic oligomers and amyloid deposits is a primary pathology in tauopathies, the most common of which is Alzheimer's disease (AD). Intrinsically disordered proteins, like tau, are enriched with proline residues that regulate both secondary structure and aggregation propensity. The orientation of proline residues is regulated by cis/trans peptidyl-prolyl isomerases (PPIases)...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28608407/disulfide-bonds-and-disorder-in-granulin-3-an-unusual-handshake-between-structural-stability-and-plasticity
#7
Gaurav Ghag, Christopher J Holler, Georgia Taylor, Thomas L Kukar, Vladimir N Uversky, Vijayaraghavan Rangachari
Granulins (GRNs) are a family of small (∼6 kDa) proteins generated by the proteolytic processing of their precursor, progranulin (PGRN), in many cell types. Both PGRN and GRNs are implicated in a plethora of biological functions, often in opposing roles to each other. Lately, GRNs have generated significant attention due to their implicated roles in neurodegenerative disorders. Despite their physiological and pathological significance, the structure-function relationships of GRNs are poorly defined. GRNs contain 12 conserved cysteines forming six intramolecular disulfide bonds, making them rather exceptional, even among a few proteins with high disulfide bond density...
June 12, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28589442/comprehensive-review-of-methods-for-prediction-of-intrinsic-disorder-and-its-molecular-functions
#8
REVIEW
Fanchi Meng, Vladimir N Uversky, Lukasz Kurgan
Computational prediction of intrinsic disorder in protein sequences dates back to late 1970 and has flourished in the last two decades. We provide a brief historical overview, and we review over 30 recent predictors of disorder. We are the first to also cover predictors of molecular functions of disorder, including 13 methods that focus on disordered linkers and disordered protein-protein, protein-RNA, and protein-DNA binding regions. We overview their predictive models, usability, and predictive performance...
September 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28589440/intrinsic-disorder-here-there-and-everywhere-and-nowhere-to-escape-from-it
#9
REVIEW
Vladimir N Uversky
The concept of protein intrinsic disorder persistently penetrates into all areas of modern protein science. It cannot be ignored anymore, and cannot be shrugged off, as it represents a vital feature (or, more correctly, a broad spectrum of important features), which, when added to and mixed with features arising from the well established protein structure-function paradigm, complete the picture of a functioning protein. The field of protein intrinsic disorder is very dynamic and fast developing. This Multi-Author Review represents a snapshot of this field by introducing some recent advances...
September 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28542206/carbonyl-based-blue-autofluorescence-of-proteins-and-amino-acids
#10
Chamani Niyangoda, Tatiana Miti, Leonid Breydo, Vladimir Uversky, Martin Muschol
Intrinsic protein fluorescence is inextricably linked to the near-UV autofluorescence of aromatic amino acids. Here we show that a novel deep-blue autofluorescence (dbAF), previously thought to emerge as a result of protein aggregation, is present at the level of monomeric proteins and even poly- and single amino acids. Just as its aggregation-related counterpart, this autofluorescence does not depend on aromatic residues, can be excited at the long wavelength edge of the UV and emits in the deep blue. Differences in dbAF excitation and emission peaks and intensities from proteins and single amino acids upon changes in solution conditions suggest dbAF's sensitivity to both the chemical identity and solution environment of amino acids...
2017: PloS One
https://www.readbyqxmd.com/read/28532244/virucidal-activity-of-cell-penetrating-peptides-of-viral-origin
#11
Nawal Abd El-Baky, Vladimir N Uversky, Elrashdy M Redwan
No abstract text is available yet for this article.
May 31, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28525284/intrinsically-disordered-proteins-as-important-players-during-desiccation-stress-of-soybean-radicles
#12
Yun Liu, Jiahui Wu, Nan Sun, Chengjian Tu, Xiaoying Shi, Hua Cheng, Simu Liu, Shuiming Li, Yong Wang, Yizhi Zheng, Vladimir N Uversky
Intrinsically disordered proteins (IDPs) play a variety of important physiological roles in all living organisms. However, there is no comprehensive analysis of the abundance of IDPs associated with environmental stress in plants. Here, we show that a set of heat-stable proteins (i.e., proteins that do not denature after boiling at 100 °C for 10 min) was present in R0mm and R15mm radicles (i.e., before radicle emergence and 15 mm long radicles) of soybean (Glycine max) seeds. This set of 795 iTRAQ-quantified heat-stable proteins contained a high proportion of wholly or highly disordered proteins (15%), which was significantly higher than that estimated for the whole soybean proteome containing 55,787 proteins (9%)...
May 30, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28504081/dissecting-physical-structure-of-calreticulin-an-intrinsically-disordered-ca-2-buffering-chaperone-from-endoplasmic-reticulum
#13
Anna Rita Migliaccio, Vladimir N Uversky
Calreticulin (CALR) is a Ca(2+) binding multifunctional protein that mostly resides in the endoplasmic reticulum (ER) and plays a number of important roles in various physiological and pathological processes. Although the major functions ascribed to CALR are controlling the Ca(2+) homeostasis in ER and acting as a lectin-like ER chaperon for many glycoproteins, this moonlighting protein can be found in various cellular compartments where it has many non-ER functions. To shed more light on the mechanisms underlying polyfunctionality of this moonlighting protein that can be found in different cellular compartments and that possesses a wide spectrum of unrelated biological activities, being able to interact with Ca(2+) (and potentially other metal ions), RNA, oligosaccharides, and numerous proteins, we used a set of experimental and computational tools to evaluate the intrinsic disorder status of CALR and the role of calcium binding on structural properties and conformational stability of the full-length CALR and its isolated P- and C-domains...
May 26, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28500420/purification-biochemical-and-structural-characterization-of-a-novel-fibrinolytic-enzyme-from-mucor-subtilissimus-ucp-1262
#14
Thiago Pajeú Nascimento, Amanda Emmanuelle Sales, Tatiana Souza Porto, Romero Marcos Pedrosa Brandão Costa, Leonid Breydo, Vladimir N Uversky, Ana Lúcia Figueiredo Porto, Attilio Converti
Fibrinolytic proteases are enzymes that degrade fibrin. They provide a promising alternative to existing drugs for thrombolytic therapy. A protease isolated from the filamentous fungus Mucor subtilissimus UCP 1262 was purified in three steps by ammonium sulfate fractionation, ion exchange, and molecular exclusion chromatographies, and characterized biochemically and structurally. The purified protease exhibited a molecular mass of 20 kDa, an apparent isoelectric point of 4.94 and a secondary structure composed mainly of α-helices...
August 2017: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/28491292/looking-at-the-recent-advances-in-understanding-%C3%AE-synuclein-and-its-aggregation-through-the-proteoform-prism
#15
REVIEW
Vladimir N Uversky
Despite attracting the close attention of multiple researchers for the past 25 years, α-synuclein continues to be an enigma, hiding sacred truth related to its structure, function, and dysfunction, concealing mechanisms of its pathological spread within the affected brain during disease progression, and, above all, covering up the molecular mechanisms of its multipathogenicity, i.e. the ability to be associated with the pathogenesis of various diseases. The goal of this article is to present the most recent advances in understanding of this protein and its aggregation and to show that the remarkable structural, functional, and dysfunctional multifaceted nature of α-synuclein can be understood using the proteoform concept...
2017: F1000Research
https://www.readbyqxmd.com/read/28480793/effect-of-human-heat-shock-protein-hspb6-on-the-solvent-features-of-water-in-aqueous-solutions
#16
Luisa A Ferreira, Nikolai B Gusev, Vladimir N Uversky, Boris Y Zaslavsky
No abstract text is available yet for this article.
May 22, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28474890/tyrosine-regulates-%C3%AE-sheet-structure-formation-in-amyloid-%C3%AE-42-a-new-clustering-algorithm-for-disordered-proteins
#17
Orkid Coskuner, Vladimir N Uversky
Our recent studies show that the single Tyr residue in the sequence of amyloid-β42 (Aβ42) is reactive toward various ligands, including metals and adenosine trisphospate (see: Coskuner , O. J. Biol. Inorg. Chem. 2016 , 21 , 957 - 973 and Coskuner , O. ; Murray , I. V. J. J. Alzheimer's Dis. 2014 , 41 , 561 - 574 ). However, the exact role of Tyr in the structures of Aβ42 remains unknown. To fill this gap, here we analyzed the role of Tyr and the impact of the Tyr10Ala mutation on the structural ensemble of Aβ42...
May 12, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28412749/diagnostic-and-prognostic-relevance-of-cp2c-and-yy1-expression-in-hepatocellular-carcinoma
#18
Ji Sook Kim, Seung Han Son, Min Young Kim, DongHo Choi, Ik-Soon Jang, Seung Sam Paik, Ji Hyung Chae, Vladimir N Uversky, Chul Geun Kim
Recent studies have demonstrated an oncogenic role of the transcription factor (TF) CP2c in hepatocellular carcinoma (HCC) based on a strong correlation between CP2c expression, tumor grade, and aggressiveness. We recently found that CP2c directly interacts with another TF, YY1, which is also overexpressed in multiple cancers, including HCC. To evaluate if these proteins are co-regulated in carcinogenesis, we analyzed the expression of CP2c and YY1 in HCC (n = 136) tissues and examined the correlation between their expression and clinicopathological characteristics of HCC...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28369666/computational-prediction-of-intrinsic-disorder-in-proteins
#19
Fanchi Meng, Vladimir Uversky, Lukasz Kurgan
Computational prediction of intrinsically disordered proteins (IDPs) is a mature research field. These methods predict disordered residues and regions in an input protein chain. More than 60 predictors of IDPs have been developed. This unit defines computational prediction of intrinsic disorder, summarizes major types of predictors of disorder, and provides details about three accurate and recently released methods. We demonstrate the use of these methods to predict intrinsic disorder for several illustrative proteins, provide insights into how predictions should be interpreted, and quantify and discuss predictive performance...
April 3, 2017: Current Protocols in Protein Science
https://www.readbyqxmd.com/read/28362316/cancer-testis-antigens-smart-biomarkers-for-diagnosis-and-prognosis-of-prostate-and-other-cancers
#20
REVIEW
Prakash Kulkarni, Vladimir N Uversky
A clinical dilemma in the management of prostate cancer (PCa) is to distinguish men with aggressive disease who need definitive treatment from men who may not require immediate intervention. Accurate prediction of disease behavior is critical because radical treatment is associated with high morbidity. Here, we highlight the cancer/testis antigens (CTAs) as potential PCa biomarkers. The CTAs are a group of proteins that are typically restricted to the testis in the normal adult but are aberrantly expressed in several types of cancers...
March 31, 2017: International Journal of Molecular Sciences
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