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Intrinsically disordered protein

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https://www.readbyqxmd.com/read/28430886/intrinsic-protein-disorder-reduces-small-scale-gene-duplicability
#1
Sanghita Banerjee, Felix Feyertag, David Alvarez-Ponce
Whereas the rate of gene duplication is relatively high, only certain duplications survive the filter of natural selection and can contribute to genome evolution. However, the reasons why certain genes can be retained after duplication whereas others cannot remain largely unknown. Many proteins contain intrinsically disordered regions (IDRs), whose structures fluctuate between alternative conformational states. Due to their high flexibility, IDRs often enable protein-protein interactions and are the target of post-translational modifications...
April 19, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28430104/dissection-of-the-interaction-between-the-intrinsically-disordered-yap-protein-and-the-transcription-factor-tead
#2
Yannick Mesrouze, Fedir Bokhovchuk, Marco Meyerhofer, Patrizia Fontana, Catherine Zimmermann, Typhaine Martin, Clara Delaunay, Dirk Erdmann, Tobias Schmelzle, Patrick Chène
TEAD (TEA/ATTS domain) transcription factors are the most distal effectors of the Hippo pathway. YAP (Yes-associated protein) is a coactivator protein which, upon binding to TEAD proteins, stimulates their transcriptional activity. Since the Hippo pathway is deregulated in various cancers, designing inhibitors of the YAP:TEAD interaction is an attractive therapeutic strategy for oncology. Understanding the molecular events that take place at the YAP:TEAD interface is therefore important not only to devise drug discovery approaches, but also to gain knowledge on TEAD regulation...
April 21, 2017: ELife
https://www.readbyqxmd.com/read/28425697/conserved-helix-flanking-prolines-modulate-idp-target-affinity-by-altering-the-lifetime-of-the-bound-complex
#3
Michael David Crabtree, Wade Borcherds, Anusha Poosapati, Sarah L Shammas, Gary W Daughdrill, Jane Clarke
Appropriate integration of cellular signals requires a delicate balance of ligand-target binding affinities. Increasing residual structure in intrinsically disordered proteins (IDPs), which are overrepresented in these cellular processes, has been shown previously to enhance binding affinities and alter cellular function. Conserved proline residues are commonly found flanking regions of IDPs that become helical upon interacting with a partner protein. Here, we mutate these helix-flanking prolines in p53 and MLL, and find opposite effects on binding affinity upon increasing free IDP helicity...
April 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28425679/soft-interactions-and-volume-exclusion-by-polymeric-crowders-can-stabilize-or-destabilize-transient-structure-in-disordered-proteins-depending-on-polymer-concentration
#4
Farai I Rusinga, David D Weis
The effects of macromolecular crowding on the transient structure of intrinsically disordered proteins is not well-understood. Crowding by biological molecules inside cells could modulate transient structure and alter IDP function. Volume exclusion theory and observations of structured proteins suggest that IDP transient structure would be stabilized by macromolecular crowding. Amide hydrogen exchange (HX) of IDPs in highly concentrated polymer solutions would provide valuable insights into IDP transient structure under crowded conditions...
April 20, 2017: Proteins
https://www.readbyqxmd.com/read/28421199/valproic-acid-protects-primary-dopamine-neurons-from-mpp-induced-neurotoxicity-involvement-of-gsk3%C3%AE-phosphorylation-by-akt-and-erk-through-the-mitochondrial-intrinsic-apoptotic-pathway
#5
Chi Zhang, Xianrui Yuan, Zhongliang Hu, Songlin Liu, Haoyu Li, Ming Wu, Jian Yuan, Zijin Zhao, Jun Su, Xiangyu Wang, Yiwei Liao, Qing Liu
Valproic acid (VPA), a drug widely used to treat manic disorder and epilepsy, has recently shown neuroprotective effects in several neurological diseases, particularly in Parkinson's disease (PD). The goal of the present study was to confirm VPA's dose-dependent neuroprotective propensities in the MPP(+) model of PD in primary dopamine (DA) neurons and to investigate the underlying molecular mechanisms using specific mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase- (PI3K-) Akt signaling inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28418268/the-folding-competence-of-hiv-1-tat-mediated-by-interaction-with-tar-rna
#6
Jung Min Kim, Hee Sun Choi, Baik Lin Seong
The trans-activator Tat protein of HIV-1 belongs to the large family of intrinsically disordered proteins (IDPs), and is known to recruit various host proteins for the transactivation of viral RNA synthesis. Tat protein interacts with the transactivator response RNA (TAR RNA), exhibiting RNA chaperone activities for structural rearrangement of interacting RNAs. Here, considering that Tat-TAR RNA interaction is mutually cooperative, we examined the potential role of TAR RNA as Chaperna - RNA that provides chaperone function to proteins - for the folding of HIV-1 Tat...
April 18, 2017: RNA Biology
https://www.readbyqxmd.com/read/28415220/multistage-modeling-of-protein-dynamics-with-monomeric-myc-oncoprotein-as-an-example
#7
Jiaojiao Liu, Jin Dai, Jianfeng He, Antti J Niemi, Nevena Ilieva
We propose to combine a mean-field approach with all-atom molecular dynamics (MD) into a multistage algorithm that can model protein folding and dynamics over very long time periods yet with atomic-level precision. As an example, we investigate an isolated monomeric Myc oncoprotein that has been implicated in carcinomas including those in colon, breast, and lungs. Under physiological conditions a monomeric Myc is presumed to be an example of intrinsically disordered proteins that pose a serious challenge to existing modeling techniques...
March 2017: Physical Review. E
https://www.readbyqxmd.com/read/28411163/development-of-a-multi-epitope-peptide-vaccine-inducing-robust-t-cell-responses-against-brucellosis-using-immunoinformatics-based-approaches
#8
Mahdiye Saadi, Ahmad Karkhah, Hamid Reza Nouri
Current investigations have demonstrated that a multi-epitope peptide vaccine targeting multiple antigens could be considered as an ideal approach for prevention and treatment of brucellosis. According to the latest findings, the most effective immunogenic antigens of brucella to induce immune responses are included Omp31, BP26, BLS, DnaK and L7-L12. Therefore, in the present study, an in silico approach was used to design a novel multi-epitope vaccine to elicit a desirable immune response against brucellosis...
April 11, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28410533/protein-aggregation-into-insoluble-deposits-protects-from-oxidative-stress
#9
Anita Carija, Susanna Navarro, Natalia Sanchez de Groot, Salvador Ventura
Protein misfolding and aggregation have been associated with the onset of neurodegenerative disorders. Recent studies demonstrate that the aggregation process can result in a high diversity of protein conformational states, however the identity of the specific species responsible for the cellular damage is still unclear. Here, we use yeast as a model to systematically analyse the intracellular effect of expressing 21 variants of the amyloid-ß-peptide, engineered to cover a continuous range of intrinsic aggregation propensities...
April 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28406453/sequence-polymorphism-and-intrinsic-structural-disorder-as-related-to-pathobiological-performance-of-the-helicobacter-pylori-caga-oncoprotein
#10
REVIEW
Hiroko Nishikawa, Masanori Hatakeyama
CagA, an oncogenic virulence factor produced by Helicobacter pylori, is causally associated with the development of gastrointestinal diseases such as chronic gastritis, peptic ulcers, and gastric cancer. Upon delivery into gastric epithelial cells via bacterial type IV secretion, CagA interacts with a number of host proteins through the intrinsically disordered C-terminal tail, which contains two repeatable protein-binding motifs, the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif and the CagA multimerization (CM) motif...
April 13, 2017: Toxins
https://www.readbyqxmd.com/read/28398197/emergence-and-evolution-of-an-interaction-between-intrinsically-disordered-proteins
#11
Greta Hultqvist, Emma Åberg, Carlo Camilloni, Gustav N Sundell, Eva Andersson, Jakob Dogan, Celestine N Chi, Michele Vendruscolo, Per Jemth
Protein-protein interactions involving intrinsically disordered proteins are important for cellular function and common in all organisms. However, it is not clear how such interactions emerge and evolve on a molecular level. We performed phylogenetic reconstruction, resurrection and biophysical characterization of two interacting disordered protein domains, CID and NCBD. CID appeared after the divergence of protostomes and deuterostomes 450-600 million years ago, while NCBD was present in the protostome/deuterostome ancestor...
April 11, 2017: ELife
https://www.readbyqxmd.com/read/28397898/nmr-probing-and-visualization-of-correlated-structural-fluctuations-in-intrinsically-disordered-proteins
#12
Dennis Kurzbach, Andreas Beier, Agathe Vanas, Andrea G Flamm, Gerald Platzer, Thomas C Schwarz, Robert Konrat
A novel statistical analysis of paramagnetic relaxation enhancement (PRE) and paramagnetic relaxation interference (PRI) based nuclear magnetic resonance (NMR) data is proposed based on the computation of correlation matrices. The technique is demonstrated with an example of the intrinsically disordered proteins (IDPs) osteopontin (OPN) and brain acid soluble protein 1 (BASP1). The correlation analysis visualizes in detail the subtleties of conformational averaging in IDPs and highlights the presence of correlated structural fluctuations of individual sub-domains in IDPs...
April 19, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28397268/optimization-of-the-gbmv2-implicit-solvent-force-field-for-accurate-simulation-of-protein-conformational-equilibria
#13
Kuo Hao Lee, Jianhan Chen
Accurate treatment of solvent environment is critical for reliable simulations of protein conformational equilibria. Implicit treatment of solvation, such as using the generalized Born (GB) class of models arguably provides an optimal balance between computational efficiency and physical accuracy. Yet, GB models are frequently plagued by a tendency to generate overly compact structures. The physical origins of this drawback are relatively well understood, and the key to a balanced implicit solvent protein force field is careful optimization of physical parameters to achieve a sufficient level of cancellation of errors...
April 11, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28394890/modeling-disordered-protein-interactions-from-biophysical-principles
#14
Lenna X Peterson, Amitava Roy, Charles Christoffer, Genki Terashi, Daisuke Kihara
Disordered protein-protein interactions (PPIs), those involving a folded protein and an intrinsically disordered protein (IDP), are prevalent in the cell, including important signaling and regulatory pathways. IDPs do not adopt a single dominant structure in isolation but often become ordered upon binding. To aid understanding of the molecular mechanisms of disordered PPIs, it is crucial to obtain the tertiary structure of the PPIs. However, experimental methods have difficulty in solving disordered PPIs and existing protein-protein and protein-peptide docking methods are not able to model them...
April 10, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28394178/a-role-of-metastable-regions-and-their-connectivity-in-the-inactivation-of-a-redox-regulated-chaperone-and-its-inter-chaperone-crosstalk
#15
Oded Rimon, Ohad Suss, Mor Goldenberg, Rosi Fassler, Ohad Yogev, Hadar Amartely, Guy Propper, Assaf Friedler, Dana Reichmann
AIMS: A recently discovered group of conditionally disordered chaperones share a very unique feature; they need to lose structure to become active as chaperones. This activation mechanism makes these chaperones particularly suited to respond to protein-unfolding stress conditions, such as oxidative unfolding. However, the role of this disorder in stress-related activation, chaperone function, and the crosstalk with other chaperone systems is not yet clear. Here, we focus on one of the members of the conditionally disordered chaperones, a thiol-redox switch of the bacterial proteostasis system, Hsp33...
April 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28393629/exploring-the-sequence-structure-function-relationship-for-the-intrinsically-disordered-%C3%AE-%C3%AE-crystallin-hahellin
#16
Meng Gao, Fei Yang, Lei Zhang, Zhengding Su, Yongqi Huang
βγ-Crystallins are a superfamily of proteins containing crystallin-type Greek key motifs. Some βγ-crystallin domains have been shown to bind Ca(2+). Hahellin is a newly identified intrinsically disordered βγ-crystallin domain from Hahella chejuensis. It folds into a typical βγ-crystallin structure upon Ca(2+) binding and acts as a Ca(2+)-regulated conformational switch. Besides Hahellin, another two putative βγ-crystallins from Caulobacter crescentus and Yersinia pestis are shown to be partially disordered in their apo-form and undergo large conformational changes upon Ca(2+) binding, although whether they acquire a βγ-crystallin fold is not known...
April 13, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28391525/regsnps-splicing-a-tool-for-prioritizing-synonymous-single-nucleotide-substitution
#17
Xinjun Zhang, Meng Li, Hai Lin, Xi Rao, Weixing Feng, Yuedong Yang, Matthew Mort, David N Cooper, Yue Wang, Yadong Wang, Clark Wells, Yaoqi Zhou, Yunlong Liu
While synonymous single-nucleotide variants (sSNVs) have largely been unstudied, since they do not alter protein sequence, mounting evidence suggests that they may affect RNA conformation, splicing, and the stability of nascent-mRNAs to promote various diseases. Accurately prioritizing deleterious sSNVs from a pool of neutral ones can significantly improve our ability of selecting functional genetic variants identified from various genome-sequencing projects, and, therefore, advance our understanding of disease etiology...
April 8, 2017: Human Genetics
https://www.readbyqxmd.com/read/28390938/natural-product-based-amyloid-inhibitors
#18
REVIEW
Paul Velander, Ling Wu, Frances Henderson, Shijun Zhang, David R Bevan, Bin Xu
Many chronic human diseases, including multiple neurodegenerative diseases, are associated with deleterious protein aggregates, also called protein amyloids. One common therapeutic strategy is to develop protein aggregation inhibitors that can slow down, prevent, or remodel toxic amyloids. Natural products are a major class of amyloid inhibitors, and several dozens of natural product-based amyloid inhibitors have been identified and characterized in recent years. These plant- or microorganism-extracted compounds have shown significant therapeutic potential from in vitro studies as well as in vivo animal tests...
April 5, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28388406/mutation-of-the-human-circadian-clock-gene-cry1-in-familial-delayed-sleep-phase-disorder
#19
Alina Patke, Patricia J Murphy, Onur Emre Onat, Ana C Krieger, Tayfun Özçelik, Scott S Campbell, Michael W Young
Patterns of daily human activity are controlled by an intrinsic circadian clock that promotes ∼24 hr rhythms in many behavioral and physiological processes. This system is altered in delayed sleep phase disorder (DSPD), a common form of insomnia in which sleep episodes are shifted to later times misaligned with the societal norm. Here, we report a hereditary form of DSPD associated with a dominant coding variation in the core circadian clock gene CRY1, which creates a transcriptional inhibitor with enhanced affinity for circadian activator proteins Clock and Bmal1...
April 6, 2017: Cell
https://www.readbyqxmd.com/read/28387819/slimsearch-a-framework-for-proteome-wide-discovery-and-annotation-of-functional-modules-in-intrinsically-disordered-regions
#20
Izabella Krystkowiak, Norman E Davey
The extensive intrinsically disordered regions of higher eukaryotic proteomes contain vast numbers of functional interaction modules known as short linear motifs (SLiMs). Here, we present SLiMSearch, a motif discovery tool that scans a motif consensus, representing the specificity determinants of a motif-binding domain, against a proteome to discover putative novel motif instances. SLiMSearch applies several distinct and complementary approaches exploiting the common properties of SLiMs to predict novel motifs...
April 6, 2017: Nucleic Acids Research
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