Occurrence of protein structure elements in conserved sequence regions

BACKGROUND: Conserved protein sequence regions are extremely useful for identifying and studying functionally and structurally important regions. By means of an integrated analysis of large-scale protein structure and sequence data, structural features of conserved protein sequence regions were identified. RESULTS: Helices and turns were found to be underrepresented in conserved regions, while strands were found to be overrepresented. Similar numbers of loops were found in conserved and random regions. CONCLUSION: These results can be understood in light of the structural constraints on different secondary structure elements, and their role in protein structural stabilization and topology. Strands can tolerate fewer sequence changes and nonetheless keep their specific shape and function. They thus tend to be more conserved than helices, which can keep their shape and function with more changes. Loop behavior can be explained by the presence of both constrained and freely changing loops in proteins. Our detailed statistical analysis of diverse proteins links protein evolution to the biophysics of protein thermodynamic stability and folding. The basic structural features of conserved sequence regions are also important determinants of protein structure motifs and their function

Ady „Minden-Titkai”

Age-related expression of the NPPB gene in heart left ventricle show overexpression in young women. Women under and above 60, n = 54 and n = 22, respectively. Men under and above 60, n = 103 and n = 39, respectively. (PDF 92 kb

ZIPK: A Unique Case of Murine-Specific Divergence of a Conserved Vertebrate Gene

Zipper interacting protein kinase (ZIPK, also known as death-associated protein kinase 3 [DAPK3]) is a Ser/Thr kinase that functions in programmed cell death. Since its identification eight years ago, contradictory findings regarding its intracellular localization and molecular mode of action have been reported, which may be attributed to unpredicted differences among the human and rodent orthologs. By aligning the sequences of all available ZIPK orthologs, from fish to human, we discovered that rat and mouse sequences are more diverged from the human ortholog relative to other, more distant, vertebrates. To test experimentally the outcome of this sequence divergence, we compared rat ZIPK to human ZIPK in the same cellular settings. We found that while ectopically expressed human ZIPK localized to the cytoplasm and induced membrane blebbing, rat ZIPK localized exclusively within nuclei, mainly to promyelocytic leukemia oncogenic bodies, and induced significantly lower levels of membrane blebbing. Among the unique murine (rat and mouse) sequence features, we found that a highly conserved phosphorylation site, previously shown to have an effect on the cellular localization of human ZIPK, is absent in murines but not in earlier diverging organisms. Recreating this phosphorylation site in rat ZIPK led to a significant reduction in its promyelocytic leukemia oncogenic body localization, yet did not confer full cytoplasmic localization. Additionally, we found that while rat ZIPK interacts with PAR-4 (also known as PAWR) very efficiently, human ZIPK fails to do so. This interaction has clear functional implications, as coexpression of PAR-4 with rat ZIPK caused nuclear to cytoplasm translocation and induced strong membrane blebbing, thus providing the murine protein a possible adaptive mechanism to compensate for its sequence divergence. We have also cloned zebrafish ZIPK and found that, like the human and unlike the murine orthologs, it localizes to the cytoplasm, and fails to bind the highly conserved PAR-4 protein. This further supports the hypothesis that murine ZIPK underwent specific divergence from a conserved consensus. In conclusion, we present a case of species-specific divergence occurring in a specific branch of the evolutionary tree, accompanied by the acquisition of a unique protein–protein interaction that enables conservation of cellular function

One-Block CYRCA: an automated procedure for identifying multiple-block alignments from single block queries

One-Block CYRCA is an automated procedure for identifying multiple-block alignments from single block queries (). It is based on the LAMA and CYRCA block-to-block alignment methods. The procedure identifies whether the query blocks can form new multiple-block alignments (block sets) with blocks from a database or join pre-existing database block sets. Using pre-computed LAMA block alignments and CYRCA sets from the Blocks database reduces the computation time. LAMA and CYRCA are highly sensitive and selective methods that can augment many other sequence analysis approaches

Refining intra-protein contact prediction by graph analysis

<p>Abstract</p> <p>Background</p> <p>Accurate prediction of intra-protein residue contacts from sequence information will allow the prediction of protein structures. Basic predictions of such specific contacts can be further refined by jointly analyzing predicted contacts, and by adding information on the relative positions of contacts in the protein primary sequence.</p> <p>Results</p> <p>We introduce a method for graph analysis refinement of intra-protein contacts, termed GARP. Our previously presented intra-contact prediction method by means of pair-to-pair substitution matrix (P2PConPred) was used to test the GARP method. In our approach, the top contact predictions obtained by a basic prediction method were used as edges to create a weighted graph. The edges were scored by a mutual clustering coefficient that identifies highly connected graph regions, and by the density of edges between the sequence regions of the edge nodes. A test set of 57 proteins with known structures was used to determine contacts. GARP improves the accuracy of the P2PConPred basic prediction method in whole proteins from 12% to 18%.</p> <p>Conclusion</p> <p>Using a simple approach we increased the contact prediction accuracy of a basic method by 1.5 times. Our graph approach is simple to implement, can be used with various basic prediction methods, and can provide input for further downstream analyses.</p

Socket preservation using deproteinized horse-derived bone mineral

Purpose: The healing process following tooth extraction apparently results in a pronounced resorption of the alveolar ridge. As a result, the width of alveolar ridge is reduced and severe alveolar bone resorption occurs. The purpose of this experiment is to clinically and histologically evaluate the results of using horse-derived bone mineral for socket preservation. Methods: The study comprised 4 patients who were scheduled for extraction as a consequence of severe chronic periodontitis or apical lesion. The extraction was followed by socket preservation using horse-derived bone minerals. Clinical parameters included buccal-palatal width, mid-buccal crest height, and mid-palatal crest height. A histologic examination was conducted. Results: The surgical sites healed uneventfully. The mean ridge width was 7.75±2.75 mm at baseline and 7.00±2.45 mm at 6 months. The ridge width exhibited no significant difference between baseline and 6 months. The mean buccal crest height at baseline was 7.5±5.20 mm, and at 6 months, 3.50±0.58 mm. The mean palatal crest height at baseline was 7.75±3.10 mm, and at 6 months, 5.00±0.82 mm. There were no significant differences between baseline and 6 months regarding buccal and palatal crest heights. The amount of newly formed bone was 9.88±2.90%, the amount of graft particles was 42.62±6.57%, and the amount of soft tissue was 47.50±9.28%. Conclusions: Socket preservation using horse-derived bone mineral can effectively maintain ridge dimensions following tooth extraction and can promote new bone formation through osteoconductive activities. Copyright © 2010 Korean Academy of Periodontology.

The Arthrobacter Species FB24 Arth_1007 (DnaB) Intein Is a Pseudogene

An Arthrobacter species FB24 gene (locus tag Arth_1007) was previously annotated as a putative intein-containing DnaB helicase of phage origin (Arsp-FB24 DnaB intein). However, it is not a helicase gene because the sequence similarity is limited to inteins. In fact, the flanking exteins total only 66 amino acids. Therefore, the intein should be referred to as the Arsp-FB24 Arth_1007 intein. The Arsp-FB24 Arth_1007 intein failed to splice in its native precursor and in a model precursor. We previously noted that the Arsp-FB24 Arth_1007 intein is the only putative Class 3 intein that is missing the catalytically essential Cys at position 4 of intein Motif F, which is one of the three defining signature residues of this class. Additionally, a catalytically essential His in position 10 of intein Motif B is also absent; this His is the most conserved residue amongst all inteins. Splicing activity was not rescued when these two catalytically important positions were ‘reverted’ back to their consensus residues. This study restores the unity of the Class 3 intein signature sequence in active inteins by demonstrating that the Arsp-FB24 Arth_1007 intein is an inactive pseudogene

Dinâmica da transmissão do Trypanosoma cruzi numa área rural da Argentina: III. Persistência da parasitemia pelo T. cruzi em reservatórios caninos durante um seguimento de dois anos

A new cross-sectional survey of household- associated mongrel dogs as well as follow-up of previously parasitemic individuals was carried out in 1984 toy means of xenodiagnosis and serologic techniques to get a deeper insight into the relationship of T. cruzi parasitemia and age among canine hosts in a rural area of Argentina. Persistence of detectable parasitemia was age-independent, or at most, loosely related to age, confirming the pattern observed in 1982. Similarly no significant age-decreasing effect was recorded among seropositive dogs in: a) the probability of detecting parasites in a 2-year follow-up; b) their intensity of infectiousness (=infective force) for T. infestans 3rd-4th instar nymphs, as measured by the percentage of infected bugs observed in each dog xenodiagnosis. Moreover, not only was the infective force of seropositive dogs for bugs approximately constant through lifetime, but it was significantly higher than the one recorded for children in the present survey, and for human people by other researchers. Therefore, and since T. infestans field populations show high feeding frequencies on dogs, the latter are expected to make the greatest contribution to the pool of infected vectors in the rural household of Argentina. This characteristic should be sufficient to involve canine reservoirs definitely as a risk factor for human people residing in the same house. The increased severity of parasitemia observed among dogs in this survey may be related to the acute undernutrition characteristic of canine populations of poor rural areas in our country, which is expected to affect the ability of the host to manage the infection.Foi realizada em 1984 uma nova pesquisa epidemiológica dos cães domésticos e seguimento dos indivíduos que apresentaram parasitemia dois anos antes a fim de compreender a relação entre a parasitemia e a idade dos cães, empregando para isso técnicas sorológicas e xenodiagnóstico. A persistência da parasitemia foi independente ou pouco relacionada à idade, confirmando assim o padrão observado em 1982. Da mesma maneira, nos cães soropositivos não se registrou nenhuma diminuição significativa com respeito a idade em: a) a probabilidade de descobrir parasitas por meio de um seguimento durante 2 anos; b) sua capacidade de infecção para as ninfas de 3.ª 4.ª fase de T. infestans, medido pela porcentagem de barbeiros infectados que se observou em cada um dos xenodiagnósticos dos cães. A capacidade infectante dos cães soropositivos foi aproximadamente constante ao longo da vida, e significativamente maior que a registrada para as crian. ças no presente estudo, e para os agrupamentos humanos pesquisados por outros investigadores. Assim sendo e considerando as altas freqüências de alimentação no cão que são observados nas populações pelo T. infestans, espera-se que o cão contribua para o total de barbeiros infectados existentes nas áreas rurais da Argentina. Esta característica deveria ser suficiente para incriminar definitivamente os reservatórios caninos como um fator de risco para as pessoas residentes na mesma casa. A alta intensidade da parasitemia registrada entre os cães na presente pesquisa poderia estar relacionada com a acentuada desnutrição característica dos cães nas áreas rurais pobres da Argentina, o que poderia afetar a capacidade do hospedeiro para controlar a infecção

Comparative statistical analysis of bacteria genomes in "word" context

Statistical analysis of bacteria genomes texts has been performed on the basis of 20 complete genomes origin from Genebank. It has been revealed that the word ranked distributions are quite well approximated by logarithmic law. Results obtained in the absent words investigation show the considerably nonrandom character of DNA texts. In character of autocorrelation function behavior in several genomes period 3 oscillations were found. Short range autocorrelations are present in short ($n=3$) words and practically absent in longer words.Comment: 14 pages, 3 figures, submitted to Physica