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Intrinsically disordered protein

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https://www.readbyqxmd.com/read/29149602/specification-of-physiologic-and-disease-states-by-distinct-proteins-and-protein-conformations
#1
REVIEW
Daniel F Jarosz, Vikram Khurana
Protein conformational states-from intrinsically disordered ensembles to amyloids that underlie the self-templating, infectious properties of prion-like proteins-have attracted much attention. Here, we highlight the diversity, including differences in biophysical properties, that drive distinct biological functions and pathologies among self-templating proteins. Advances in chemical genomics, gene editing, and model systems now permit deconstruction of the complex interplay between these protein states and the host factors that react to them...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29140585/timap-the-versatile-protein-phosphatase-1-regulator-in-endothelial-cells
#2
REVIEW
Anita Boratkó, Csilla Csortos
Transforming growth factor (TGF)-β inhibited membrane associated protein, TIMAP, is the member of the myosin phosphatase targeting protein (MYPT) family of protein phosphatase 1 (PP1) regulatory subunits. The N-terminal part of TIMAP has a typical MYPT family structure with a sequence element called MyPhone (myosin phosphatase N-terminal element), a putative bipartite nuclear localization signal, a PP1 catalytic subunit binding motif, and five ankyrin repeats. The C-terminal half of TIMAP is intrinsically disordered, but ends with a functional CAAX box for lipid modification which allows localization of TIMAP at the plasma membrane...
November 15, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29140480/the-intrinsically-disordered-n-terminal-arm-of-the-brome-mosaic-virus-coat-protein-specifically-recognizes-the-rna-motif-that-directs-the-initiation-of-viral-rna-replication
#3
Alexander Jacobs, Haley Hoover, Edward Smith, David E Clemmer, Chul-Hyun Kim, C Cheng Kao
In the brome mosaic virus (BMV) virion, the coat protein (CP) selectively contacts the RNA motifs that regulate translation and RNA replication (Hoover et al., 2016. J. Virol. 90, 7748). We hypothesize that the unstructured N-terminal arm (NTA) of the BMV CP can specifically recognize RNA motifs. Using ion mobility spectrometry-mass spectrometry, we demonstrate that peptides containing the NTA of the CP were found to preferentially bind to an RNA hairpin motif that directs the initiation of BMV RNA synthesis...
November 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29138501/targeting-sxip-eb1-interaction-an-integrated-approach-to-the-discovery-of-small-molecule-modulators-of-dynamic-binding-sites
#4
T B Almeida, A J Carnell, I L Barsukov, N G Berry
End binding protein 1 (EB1) is a key element in the complex network of protein-protein interactions at microtubule (MT) growing ends, which has a fundamental role in MT polymerisation. EB1 is an important protein target as it is involved in regulating MT dynamic behaviour, and has been associated with several disease states, such as cancer and neuronal diseases. Diverse EB1 binding partners are recognised through a conserved four amino acid motif, (serine-X-isoleucine-proline) which exists within an intrinsically disordered region...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138428/structural-disorder-and-induced-folding-within-two-cereal-aba-stress-and-ripening-asr-proteins
#5
Karama Hamdi, Edoardo Salladini, Darragh P O'Brien, Sébastien Brier, Alexandre Chenal, Ines Yacoubi, Sonia Longhi
Abscisic acid (ABA), stress and ripening (ASR) proteins are plant-specific proteins involved in plant response to multiple abiotic stresses. We previously isolated the ASR genes and cDNAs from durum wheat (TtASR1) and barley (HvASR1). Here, we show that HvASR1 and TtASR1 are consistently predicted to be disordered and further confirm this experimentally. Addition of glycerol, which mimics dehydration, triggers a gain of structure in both proteins. Limited proteolysis showed that they are highly sensitive to protease degradation...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29136219/mobidb-3-0-more-annotations-for-intrinsic-disorder-conformational-diversity-and-interactions-in-proteins
#6
Damiano Piovesan, Francesco Tabaro, Lisanna Paladin, Marco Necci, Ivan Micetic, Carlo Camilloni, Norman Davey, Zsuzsanna Dosztányi, Bálint Mészáros, Alexander M Monzon, Gustavo Parisi, Eva Schad, Pietro Sormanni, Peter Tompa, Michele Vendruscolo, Wim F Vranken, Silvio C E Tosatto
The MobiDB (URL: mobidb.bio.unipd.it) database of protein disorder and mobility annotations has been significantly updated and upgraded since its last major renewal in 2014. Several curated datasets for intrinsic disorder and folding upon binding have been integrated from specialized databases. The indirect evidence has also been expanded to better capture information available in the PDB, such as high temperature residues in X-ray structures and overall conformational diversity. Novel nuclear magnetic resonance chemical shift data provides an additional experimental information layer on conformational dynamics...
November 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29133811/site-specific-phosphorylation-regulates-the-structure-and-function-of-an-intrinsically-disordered-domain-of-the-glucocorticoid-receptor
#7
Shagufta H Khan, William A McLaughlin, Raj Kumar
Intrinsically disordered (ID) regions of the transcription factor proteins have much larger frequency of phosphorylation sites than ordered regions, suggesting an important role in their regulatory capacity. Consistent with this phenomenon, most of the functionally known phosphorylation sites in the steroid receptor family of transcription factors are located in the ID N-terminal domain that contains a powerful activation function (AF1) region. In this study, we determined the structural and functional consequences of functionally known phosphorylation residues (Ser203, 211, and 226) located in the human glucocorticoid receptor's (GR's) ID AF1 domain...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29129703/identification-of-novel-mitochondrial-localization-signals-in-human-tafazzin-the-cause-of-the-inherited-cardiomyopathic-disorder-barth-syndrome
#8
Ana A Dinca, Wei-Ming Chien, Michael T Chin
Mutations in the gene tafazzin (TAZ) result in Barth syndrome (BTHS). Patients present with hypotonia, cyclic neutropenia, 3-methyglutaconic aciduria, and cardiomyopathy, which is the major cause of mortality. The recessive, X-linked TAZ gene encodes a mitochondrial membrane-associated phospholipid modifying enzyme, which adds unsaturated fatty acid species to monolysocardiolipin to generate mature cardiolipin in the mitochondrial membrane that is essential for mitochondrial morphology and function. To identify intrinsic mitochondrial localization sequences in the human TAZ protein, we made sequential TAZ peptide-eGFP fusion protein expression constructs and analyzed the localization of eGFP fluorescence by confocal microscopy...
November 10, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29127738/concerted-millisecond-timescale-dynamics-in-the-intrinsically-disordered-carboxyl-terminus-of-%C3%AE-tubulin-induced-by-mutation-of-a-conserved-tyrosine-residue
#9
Jason Harris, Maria Shadrina, Carlos Oliver, Jackie Vogel, Anthony Mittermaier
Tubulins are an ancient family of eukaryotic proteins characterized by an amino-terminal globular domain and disordered carboxyl terminus. These carboxyl termini play important roles in modulating the behavior of microtubules in living cells. However, the atomic-level basis of their function is not well understood. These regions contain multiple acidic residues and their overall charges are modulated in vivo by post-translational modifications, e.g. phosphorylation. In this study, we describe an application of NMR and computer Monte Carlo simulations to investigate how the modification of local charge alters the conformational sampling of the γ-tubulin carboxyl terminus...
November 11, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29124793/evidence-for-allosteric-effects-on-p53-oligomerization-induced-by-phosphorylation
#10
Petr Muller, Juliana M Chan, Oliver Simoncik, Miroslav Fojta, David P Lane, Ted Hupp, Borivoj Vojtesek
P53 is a tetrameric protein with a thermodynamically unstable DNA-binding domain flanked by intrinsically disordered regulatory domains that control its activity. The unstable and disordered segments of p53 allow high flexibility as it interacts with binding partners and permits a rapid on/off switch to control its function. The p53 tetramer can exist in multiple conformational states, any of which can be stabilized by a particular modification. Here, we apply the allostery model to p53 to ask whether evidence can be found that the "activating" C-terminal phosphorylation of p53 stabilizes a specific conformation of the protein in the absence of DNA...
November 10, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29124689/xeroderma-pigmentosa-group-a-xpa-nucleotide-excision-repair-and-regulation-by-atr-in-response-to-ultraviolet-irradiation
#11
Phillip R Musich, Zhengke Li, Yue Zou
The sensitivity of Xeroderma pigmentosa (XP) patients to sunlight has spurred the discovery and genetic and biochemical analysis of the eight XP gene products (XPA-XPG plus XPV) responsible for this disorder. These studies also have served to elucidate the nucleotide excision repair (NER) process, especially the critical role played by the XPA protein. More recent studies have shown that NER also involves numerous other proteins normally employed in DNA metabolism and cell cycle regulation. Central among these is ataxia telangiectasia and Rad3-related (ATR), a protein kinase involved in intracellular signaling in response to DNA damage, especially DNA damage-induced replicative stresses...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29115597/quantitative-proteomic-study-of-the-plasma-reveals-acute-phase-response-and-lxr-rxr-and-fxr-rxr-activation-in-the-chronic-unpredictable-mild-stress-mouse-model-of-depression
#12
Chuangchuang Yang, Chanjuan Zhou, Jie Li, Zhi Chen, Haiyang Shi, Wensong Yang, Yinhua Qin, Lin Lü, Libo Zhao, Liang Fang, Haiyang Wang, Zicheng Hu, Peng Xie
Major depressive disorder is a severe neuropsychiatric disease that negatively impacts the quality of life of a large portion of the population. However, the molecular mechanisms underlying depression are still unclear. The pathogenesis of depression involves several brain regions. However, most previous studies have focused only on one specific brain region. Plasma and brain tissues exchange numerous components through the blood‑brain barrier. Therefore, in the present study, plasma samples from control (CON) mice and mice subjected to chronic unpredictable mild stress (CUMS) were used to investigate the molecular pathogenesis of depression, and the association between the peripheral circulation and the central nervous system...
October 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29114050/structure-and-function-of-yeast-atg20-a-sorting-nexin-that-facilitates-autophagy-induction
#13
Hana Popelka, Alejandro Damasio, Jenny E Hinshaw, Daniel J Klionsky, Michael J Ragusa
The Atg20 and Snx4/Atg24 proteins have been identified in a screen for mutants defective in a type of selective macroautophagy/autophagy. Both proteins are connected to the Atg1 kinase complex, which is involved in autophagy initiation, and bind phosphatidylinositol-3-phosphate. Atg20 and Snx4 contain putative BAR domains, suggesting a possible role in membrane deformation, but they have been relatively uncharacterized. Here we demonstrate that, in addition to its function in selective autophagy, Atg20 plays a critical role in the efficient induction of nonselective autophagy...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29110341/hemin-and-bile-pigments-are-the-secondary-structure-regulators-of-intrinsically-disordered-antimicrobial-peptides
#14
Ferenc Zsila, Tünde Juhász, Szilvia Bősze, Kata Horváti, Tamás Beke-Somfai
The interaction of protoporphyrin compounds of human origin with the major bee venom component melittin (26 a.a., Z +6) and its hybrid derivative (CM15, 15 a.a., Z +6) were studied by a combination of various spectroscopic methods. Throughout a two-state, concentration-dependent process, hemin and its metabolites (biliverdin, bilirubin, bilirubin ditaurate) increase the parallel β-sheet content of the natively unfolded melittin, suggesting the oligomerization of the peptide chains. In contrast, α-helix promoting effect was observed with the also disordered but more cationic CM15...
November 7, 2017: Chirality
https://www.readbyqxmd.com/read/29104751/conformation-dynamics-of-the-intrinsically-disordered-protein-c-myb-with-the-ff99idps-force-field
#15
Xiang Guo, Jincheng Han, Ray Luo, Hai-Feng Chen
The intrinsically disordered protein c-Myb plays a critical role in cellular proliferation and differentiation. Loss of c-myb function results in embryonic lethality due to failure of fetal hepatic hematopoiesis. The conformation dynamics of the intrinsically disordered c-Myb are still unknown. Here, molecular dynamics (MD) simulations with the intrinsically disordered protein force field ff99IDPs were used to study the conformation dynamics. In comparison with ff99SBildn, ff99IDPs can reproduce more diverse disordered conformers of c-Myb...
2017: RSC Advances
https://www.readbyqxmd.com/read/29102725/structural-modeling-of-osteoarthritis-adamts4-complex-with-its-cognate-inhibitory-protein-timp3-and-rational-derivation-of-cyclic-peptide-inhibitors-from-the-complex-interface-to-target-adamts4
#16
Wei Zhang, Biao Zhong, Chi Zhang, Yukai Wang, Shang Guo, Congfeng Luo, Yulin Zhan
The ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) enzyme is a matrix-associated zinc metalloendopeptidase that plays an essential role in the degradation of cartilage aggrecan in arthritic diseases and has been recognized as one of the most primary targets for therapeutic intervention in osteoarthritis (OA). Here, we reported computational modeling of the atomic-level complex structure of ADAMTS4 with its cognate inhibitory protein TIMP3 based on high-resolution crystal template...
November 2, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29100606/bh3-only-protein-bim-an-emerging-target-in-chemotherapy
#17
REVIEW
Shatrunajay Shukla, Sugandh Saxena, Brijesh Kumar Singh, Poonam Kakkar
BH3-only proteins constitute major proportion of pro-apoptotic members of B-cell lymphoma 2 (Bcl-2) family of apoptotic regulatory proteins and participate in embryonic development, tissue homeostasis and immunity. Absence of BH3-only proteins contributes to autoimmune disorders and tumorigenesis. Bim (Bcl-2 Interacting Mediator of cell death), most important member of BH3-only proteins, shares a BH3-only domain (9-16 aa) among 4 domains (BH1-BH4) of Bcl-2 family proteins and highly pro-apoptotic in nature...
September 23, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29100108/complex-regulatory-mechanisms-mediated-by-the-interplay-of-multiple-post-translational-modifications
#18
REVIEW
Veronika Csizmok, Julie D Forman-Kay
Post-translational modifications (PTMs), which are found largely in intrinsically disordered protein regions (IDRs), regulate protein activity, stability and interactions with partners. They are therefore critical for controlling essentially all cellular processes. A single modification event can have dramatic effects; however, proteins are often modified on multiple sites to collectively modulate the biological outcome. Multiple PTMs can mediate the same, complementary or opposing effects and the result of their interplay is determined by a complex combination of the number, positioning and type of modifications...
October 31, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29098540/multiscale-persistent-functions-for-biomolecular-structure-characterization
#19
Kelin Xia, Zhiming Li, Lin Mu
In this paper, we introduce multiscale persistent functions for biomolecular structure characterization. The essential idea is to combine our multiscale rigidity functions (MRFs) with persistent homology analysis, so as to construct a series of multiscale persistent functions, particularly multiscale persistent entropies, for structure characterization. To clarify the fundamental idea of our method, the multiscale persistent entropy (MPE) model is discussed in great detail. Mathematically, unlike the previous persistent entropy (Chintakunta et al...
November 2, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/29097748/kixbase-a-comprehensive-web-resource-for-identification-and-exploration-of-kix-domains
#20
Archana Yadav, Jitendra K Thakur, Gitanjali Yadav
The KIX domain has emerged in the last two decades as a critical site of interaction for transcriptional assembly, regulation and gene expression. Discovered in 1994, this conserved, triple helical globular domain has been characterised in various coactivator proteins of yeast, mammals and plants, including the p300/CBP (a histone acetyl transferase), MED15 (a subunit of the mediator complex of RNA polymerase II), and RECQL5 helicases. In this work, we describe the first rigorous meta analysis of KIX domains across all forms of life, leading to the development of KIXBASE, a predictive web server and global repository for detection and analysis of KIX domains...
November 2, 2017: Scientific Reports
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