protein sequence patterns
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... Motifs of Protein Structure -- Few general principles emerged from the first protein structure -- The ... ... reflects p structure 62 -- The retinol-binding protein belongs to a superfamily of protein structures ... ... protein-DNA interactions recognize operator regions 96 -- Nonspecific protein-DNA interactions determine ... ... related 100 -- Cro and repressor have homologous sequences but partly different structures 101 -- Sequence ... ... are molecular amplifiers 222 -- G proteins are homologous in sequence to elongation factor Tu and cH-ras ...
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Lx mutation in SHR.Lx rat manifests in homozygotes as hindlimb preaxial polydactyly. It was previously mapped to a chromosome 8 segment containing the Plzf gene. Plzf (promyelocytic leukemia zinc finger protein) influences limb development as a direct repressor of posterior HoxD genes. However, the Plzf coding sequence is intact in the Lx mutants. Using linkage mapping in F2 hybrids, we downsized the segment containing Lx to 155 kb and sequenced conserved noncoding elements (CNEs) inside. A 2,964-bp deletion in Plzf intron 2, never detected in control animals, is the only candidate for Lx. The deletion removes the most deeply conserved CNE in the 155-kb segment, suggesting a regulatory influence on Plzf expression. Correspondingly, using in situ hybridization and quantitative real-time polymerase chain reaction, we found a decrease of Plzf expression in Lx/Lx limb buds with concomitant anterior expansion of expression domains of its targets, Hoxd10-13 genes, in the absence of ectopic Sonic hedgehog expression. Upstream regulation of Plzf in limb buds is currently unknown. We present here the first candidate Plzf cis-regulatory sequence. (c) 2009 Wiley-Liss, Inc.
- MeSH
- delece genu MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- down regulace genetika MeSH
- embryo savčí embryologie metabolismus MeSH
- financování organizované MeSH
- introny genetika MeSH
- končetinové pupeny abnormality metabolismus MeSH
- konzervovaná sekvence MeSH
- krysa rodu rattus MeSH
- messenger RNA genetika MeSH
- nekódující RNA genetika MeSH
- polydaktylie genetika metabolismus MeSH
- rozvržení tělního plánu MeSH
- sekvence nukleotidů MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
Well defined biomacromolecular patterns such as binding sites, catalytic sites, specific protein or nucleic acid sequences, etc. precisely modulate many important biological phenomena. We introduce PatternQuery, a web-based application designed for detection and fast extraction of such patterns. The application uses a unique query language with Python-like syntax to define the patterns that will be extracted from datasets provided by the user, or from the entire Protein Data Bank (PDB). Moreover, the database-wide search can be restricted using a variety of criteria, such as PDB ID, resolution, and organism of origin, to provide only relevant data. The extraction generally takes a few seconds for several hundreds of entries, up to approximately one hour for the whole PDB. The detected patterns are made available for download to enable further processing, as well as presented in a clear tabular and graphical form directly in the browser. The unique design of the language and the provided service could pave the way towards novel PDB-wide analyses, which were either difficult or unfeasible in the past. The application is available free of charge at http://ncbr.muni.cz/PatternQuery.
Inaktivace genu p53mutací je jednímz nejčastěji se vyskytujících genetických jevů u lidských nádorů, což poukazuje na centrální úlohu p53 jako nádorového supresoru. Funkční protein p53 působí jako silný transkripční faktor vážící se na minimálně 300 různých promotorových sekvencí v genomu. Jako transkripční faktor může p53 široce měnit profil specifické genové exprese, což vede k zástavě buněčného cyklu a/nebo k apoptóze. Transkripční aktivita proteinu p53 je velmi přísně regulována a její bazální aktivita je zvýšena v buňkách vystavených široké škále stresových faktorů. Stresem regulovaná transaktivační funkce p53 je řízena jeho sekvenčně specifickou DNA-vazebnou doménou a je koordinována specifickými protein-proteinovými interakcemi, které mohou být modulovány kovalentními a nekovalentními modifikacemi. Mutantní formy proteinu p53 jsou defektní v sekvenčně specifické vazbě na DNA, neboť mutace měnící smysl kodonu ovlivňují základní vlastnosti proteinu. Analýzy mutovaných p53 ukázaly, že existují různé konformační třídy mutantů a že reaktivace každé z těchto tříd vyžaduje odlišnou strategii závisející namechanizmu vzniku chybné konformace proteinu p53. Potenciální aktivace nemutovaného i mutovaného proteinu p53 in vivo vzbuzuje naději na vývoj protinádorových léčiv použitelných k léčbě rakoviny v kombinaci se sofistikovanou diagnostikou.
Mutational inactivation of the p53 gene products is one of the most common genetic events that occur in human cancer confirming the central role of p53 as a tumour suppressor. The wild type p53 protein acts as a powerful transcription factor binding as many as 300 different promoter sequences in the genome. As a transcription factor, p53 can broadly alter patterns of specific gene expression leading to cell-cycle arrest and/or apoptosis. The transcriptional activity of the p53 protein is precisely regulated and its basal activity is enhanced in cells exposed to a wide variety of stress signals. This stress regulated transactivation function of p53 is driven by its sequence-specific DNA-binding domain and is co-ordinated by specific protein-protein interactions that can be modulated by covalent and non-covalent modifications. The mutant forms of p53 protein are defective in sequence specific DNA-binding because the missense mutation affects one or all of the assembly pathways. Analysis of p53 mutant has shown that different conformational classes of mutants exist and the reactivation of each class requires a different strategy depending on the mechanism of p53 protein misfolding. Potential reactivation of both wild type and mutant p53 protein in vivo raises our hopes of developing anti-cancer drugs useful in combination with sophisticated diagnostics for the treatment of cancer.
Experimental cDNA sequence determinations lag behind in silico gene structure predictions in some recently sequenced genomes. This may be due in part to low transcript abundance and/or the severely spatio-temporarily restricted expression pattern of some genes. Here we characterize the predicted repressed gene of Arabidopsis thaliana (At4g21130) that encodes a homologue of the Arabidopsis U3-55K-like protein (At4g05410) and of the U3-55K (RNU3IP2, Rrp9p) proteins from other eukaryotes. In man and yeast, U3-55K is involved in the processing of the pre-ribosomal RNA. Here we show that treatment with inhibitors of histone deacetylases (trichostatin A, sodium butyrate) or DNA methyltransferases (5-aza-2'-deoxycytidine) induces a low but distinct level of mRNA from the repressed Arabidopsis At4g21130 locus, which can be detected by RT-PCR amplification. Direct sequencing of PCR products reveals the open reading frame that differs, in part, from the hypothetical one and encodes a seven-WD-repeat protein highly conserved when compared to U3-55K proteins from various eukaryotic species. This suggests the conservation of its function. The described approach may help to determine the nucleotide sequences of transcripts from predicted genes with a low level of expression.
- MeSH
- Arabidopsis genetika metabolismus MeSH
- financování organizované MeSH
- histondeacetylasy metabolismus MeSH
- inhibitory enzymů farmakologie MeSH
- inhibitory histondeacetylas MeSH
- klonování DNA MeSH
- komplementární DNA genetika MeSH
- lokus kvantitativního znaku genetika MeSH
- molekulární sekvence - údaje MeSH
- posttranskripční úpravy RNA genetika MeSH
- proteiny huseníčku genetika metabolismus MeSH
- regulace genové exprese u rostlin fyziologie účinky léků MeSH
- ribonukleoproteiny malé jadérkové genetika metabolismus MeSH
- RNA ribozomální metabolismus MeSH
- sekvence aminokyselin MeSH
- sekvenční analýza DNA metody MeSH
- sekvenční analýza proteinů metody MeSH
- sekvenční homologie aminokyselin MeSH
Myotonic dystrophy type 1 is caused by the expansion of a CTG repeat in the 3' UTR of the DMPK gene. A length exceeding 50 CTG triplets is pathogenic. Intermediate alleles with 35-49 triplets are not disease-causing but show instability in intergenerational transmissions. We report on the identification of multiple patients with different patterns of CCG and CTC interruptions in the DMPK CTG repeat tract that display unique intergenerational instability. In patients bearing interrupted expanded alleles, the location of the interruptions changed dramatically between generations and the repeats tended to contract. The phenotype for these patients corresponded to the classical form of the disease, but in some cases without muscular dystrophy and possibly with a later onset than expected. Symptomatic patients bearing interrupted intermediate length repeat tracts were also identified, although the role of the interruptions in their phenotype remains unclear. The identification of interruptions in the DMPK repeat has important consequences for molecular genetic testing where they can lead to false negative conclusions.
- MeSH
- delece genu MeSH
- dospělí MeSH
- frekvence genu MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mutační analýza DNA MeSH
- nestabilita genomu MeSH
- protein-serin-threoninkinasy genetika MeSH
- rodina MeSH
- rodokmen MeSH
- sekvence nukleotidů MeSH
- studie případů a kontrol MeSH
- trinukleotidové repetice genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
A systematic search for expressed sequences in the human Xq28 region resulted in the isolation of 8.5 kb large contigs of human and murine cDNAs with no apparent conserved open reading frames. These cDNAs were found to be derived from the 3"-untranslated region (3"-UTR) of the methyl-CpG-binding protein 2 gene ( MeCP2 ). This long 3"-UTR is part of an alternatively polyadenylated, 10.1 kb MeCP2 transcript which is differentially expressed in human brain and other tissues. RNA in situ hybridization to sections of mouse embryo and adult tissues of an Mecp2 3"-UTR probe showed ubiquitous low level expression in early organogenesis and enhanced expression in the hippocampus during formation of the differentiated brain. Sequence comparison between the human and mouse homologues revealed several blocks of very high conservation separated by less conserved sequences. Additional support for a domain-like conservation pattern of the long 3"-UTR of the MeCP2 gene was obtained by examining conservation in the chimpanzee, orangutan, macaque, hamster, rat and kangaroo. The minimum free energy distribution for the predicted RNA secondary structure was very similar in human and mouse sequences. In particular, the conserved blocks were predicted to be of high minimum free energy, which suggests weak secondary structure with respect to RNA folding. The fact that both the sequence and predicted secondary structure have been highly conserved during evolution suggests that both the primary sequence and the three-dimensional structure of the 3"-UTR may be important for its function in post-transcriptional regulation of MeCP2 expression.
- MeSH
- 3' nepřekládaná oblast * MeSH
- adenin * metabolismus MeSH
- chromozomální proteiny, nehistonové * MeSH
- DNA vazebné proteiny * genetika MeSH
- fylogeneze MeSH
- genetická variace MeSH
- konformace nukleové kyseliny MeSH
- konzervovaná sekvence MeSH
- křečci praví MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- molekulární evoluce MeSH
- molekulární sekvence - údaje MeSH
- myši MeSH
- protein 2 vázající methyl-CpG MeSH
- regulace genové exprese * MeSH
- represorové proteiny * MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA MeSH
- sekvenční homologie nukleových kyselin MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Amino acid sequence and environment are the most important factors determining the structure, stability and dynamics of proteins. To evaluate their roles in the process of folding, we studied a retroversion of the well-described Trp-cage miniprotein in water and 2,2,2-trifluoroethanol (TFE) solution. We show, by circular dichroism spectroscopy and nuclear magnetic resonance (NMR) measurement, that the molecule has no stable structure under conditions in which the Trp-cage is folded. A detectable stable structure of the retro Trp-cage, with the architecture similar to that of the original Trp-cage, is established only upon addition of TFE to 30% of the total solvent volume. The retro Trp-cage structure shows a completely different pattern of stabilizing contacts between amino acid residues, involving the guanidinium group of arginine and the aromatic group of tryptophan. The commonly used online prediction methods for protein and peptide structures Robetta and PEP-FOLD failed to predict that the retro Trp-cage is unstructured under default prediction conditions. On the other hand, both methods provided structures with a fold similar to those of the experimentally determined NMR structure in water/TFE but with different contacts between amino acids.
- MeSH
- arginin chemie MeSH
- molekulární sekvence - údaje MeSH
- peptidy chemická syntéza chemie MeSH
- sbalování proteinů MeSH
- sekundární struktura proteinů MeSH
- sekvence aminokyselin MeSH
- simulace molekulární dynamiky MeSH
- stabilita proteinů MeSH
- statická elektřina MeSH
- termodynamika MeSH
- trifluorethanol chemie MeSH
- tryptofan chemie MeSH
- voda chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Complementary molecules on the surface of both gametes are responsible for the interaction of sperm protein receptors with zona pellucida (ZP) saccharide structures, and many primary sperm receptors for ZP glycoproteins have been disclosed in various mammals. For our study, proteins were obtained from the surface of ejaculated and in vitro capacitated boar sperm. The isolated proteins were characterized by 1D- and 2D-electrophoretic protein profiles, and by glycoprotein staining. Our results show quantitative and qualitative differences in protein and glycoprotein patterns between ejaculated and capacitated sperm. Far-western blotting with ZP glycoproteins identified 17 interactions in the subproteome of the ejaculated sperm and 14 interactions in the subproteome of the capacitated sperm. High-molecular-mass proteins, coincident with binding to ZP, were sequence-identified. Angiotensin-converting enzyme (ACE), polycystic kidney disease receptor and egg jelly receptor (PKDREJ), and acrosin precursor were successfully identified. This is the first time PKDREJ has been identified on the surface of boar spermatozoa.
- MeSH
- hmotnostní spektrometrie MeSH
- kapacitace spermií * MeSH
- membránové glykoproteiny metabolismus MeSH
- membránové proteiny metabolismus MeSH
- myši MeSH
- proteom MeSH
- proteomika metody MeSH
- spermie metabolismus MeSH
- Sus scrofa MeSH
- vazba proteinů MeSH
- zona pellucida metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Protein-protein interactions (PPI) play a key role in an investigation of various biochemical processes, and their identification is thus of great importance. Although computational prediction of which amino acids take part in a PPI has been an active field of research for some time, the quality of in-silico methods is still far from perfect. RESULTS: We have developed a novel prediction method called INSPiRE which benefits from a knowledge base built from data available in Protein Data Bank. All proteins involved in PPIs were converted into labeled graphs with nodes corresponding to amino acids and edges to pairs of neighboring amino acids. A structural neighborhood of each node was then encoded into a bit string and stored in the knowledge base. When predicting PPIs, INSPiRE labels amino acids of unknown proteins as interface or non-interface based on how often their structural neighborhood appears as interface or non-interface in the knowledge base. We evaluated INSPiRE's behavior with respect to different types and sizes of the structural neighborhood. Furthermore, we examined the suitability of several different features for labeling the nodes. Our evaluations showed that INSPiRE clearly outperforms existing methods with respect to Matthews correlation coefficient. CONCLUSION: In this paper we introduce a new knowledge-based method for identification of protein-protein interaction sites called INSPiRE. Its knowledge base utilizes structural patterns of known interaction sites in the Protein Data Bank which are then used for PPI prediction. Extensive experiments on several well-established datasets show that INSPiRE significantly surpasses existing PPI approaches.
