Discrimination between biological interfaces and crystal-packing contacts

A discrimination method between biologically relevant interfaces and artificial crystal-packing contacts in crystal structures was constructed. The method evaluates protein-protein interfaces in terms of complementarities for hydrophobicity, electrostatic potential and shape on the protein surfaces, and chooses the most probable biological interfaces among all possible contacts in the crystal. The method uses a discriminator named as “COMP”, which is a linear combination of the complementarities for the above three surface features and does not correlate with the contact area. The discrimination of homo-dimer interfaces from symmetry-related crystal-packing contacts based on the COMP value achieved the modest success rate. Subsequent detailed review of the discrimination results raised the success rate to about 88.8%. In addition, our discrimination method yielded some clues for understanding the interaction patterns in several examples in the PDB. Thus, the COMP discriminator can also be used as an indicator of the “biological-ness” of protein-protein interfaces

eF-seek: prediction of the functional sites of proteins by searching for similar electrostatic potential and molecular surface shape

We have developed a method to predict ligand-binding sites in a new protein structure by searching for similar binding sites in the Protein Data Bank (PDB). The similarities are measured according to the shapes of the molecular surfaces and their electrostatic potentials. A new web server, eF-seek, provides an interface to our search method. It simply requires a coordinate file in the PDB format, and generates a prediction result as a virtual complex structure, with the putative ligands in a PDB format file as the output. In addition, the predicted interacting interface is displayed to facilitate the examination of the virtual complex structure on our own applet viewer with the web browser (URL: http://eF-site.hgc.jp/eF-seek)

PreBI: prediction of biological interfaces of proteins in crystals

PreBI is a server that predicts biological interfaces in protein crystal structures, according to the complementarity and the area of the interface. The server accepts a coordinate file in the PDB format, and all of the possible interfaces are generated automatically, according to the symmetry operations given in the coordinate file. For all of the interfaces generated, the complementarities of the electrostatic potential, hydrophobicity and shape of the interfaces are analyzed, and the most probable biological interface is identified according to the combination of the degree of complementarity derived from the database analyses and the area of the interface. The results can be checked through an interactive viewer, and the most probable complex can be downloaded as atomic coordinates in the PDB format. PreBI is available at

Weak correlation between sequence conservation in promoter regions and in protein-coding regions of human-mouse orthologous gene pairs

<p>Abstract</p> <p>Background</p> <p>Interspecies sequence comparison is a powerful tool to extract functional or evolutionary information from the genomes of organisms. A number of studies have compared protein sequences or promoter sequences between mammals, which provided many insights into genomics. However, the correlation between protein conservation and promoter conservation remains controversial.</p> <p>Results</p> <p>We examined promoter conservation as well as protein conservation for 6,901 human and mouse orthologous genes, and observed a very weak correlation between them. We further investigated their relationship by decomposing it based on functional categories, and identified categories with significant tendencies. Remarkably, the 'ribosome' category showed significantly low promoter conservation, despite its high protein conservation, and the 'extracellular matrix' category showed significantly high promoter conservation, in spite of its low protein conservation.</p> <p>Conclusion</p> <p>Our results show the relation of gene function to protein conservation and promoter conservation, and revealed that there seem to be nonparallel components between protein and promoter sequence evolution.</p

Extended asymmetry model based on logit transformation and decomposition of symmetry for square contingency tables with ordered categories

The issues of symmetry (or asymmetry) arises naturally for the analysis of square contingency tables. Many existing asymmetry models do not have the constraints on the main diagonal cells. Thus, the observations on the main diagonal cells do not contribute to the likelihood ratio chi-squared test statistics. Herein we propose a model that indicates the asymmetry for the log odds.It can utilize the information in the main diagonal cells. Also, the symmetry model is separated into some models including the proposed model

DBTGR: a database of tunicate promoters and their regulatory elements

The high similarity of tunicates and vertebrates during their development coupled with the transparency of tunicate larvae, their well-studied cell lineages and the availability of simple and efficient transgenesis methods makes of this subphylum an ideal system for the investigation of vertebrate physiological and developmental processes. Recently, the sequencing of two different Ciona genomes has lead to the identification of numerous genes. In order to better understand the regulation of these genes, a database was created containing information on regulation of tunicate genes collected from literature. It includes for instance information regarding the minimal promoter length, the transcription factors involved and their binding sites, as well as the localization of the gene expression. Additionally, binding sites for characterized transcription factors were predicted based on published in vitro recognition sites. Comparison of the promoters of homologous genes in different species is also provided to allow identification of conserved cis elements. At the time of writing, information about 184 promoters, containing 73 identified binding sites and >2000 newly predicted binding sites is available. This database is accessible at

Insulin regulates Presenilin 1 localization via PI3K/Akt signaling.

Recently, insulin signaling has been highlighted in the pathology of Alzheimer's disease (AD). Although the association between insulin signaling and Tau pathology has been investigated in several studies, the interaction between insulin signaling and Presenilin 1 (PS1), a key molecule of amyloid beta (Abeta) pathology, has not been elucidated so far. In this study, we demonstrated that insulin inhibited PS1 phosphorylation at serine residues (serine 353, 357) via phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway and strengthened the trimeric complex of PS1/N-cadherin/beta-catenin, consequently relocalizing PS1 to the cell surface. Since our recent report suggests that PS1/N-cadherin/beta-catenin complex regulates Abeta production, it is likely that insulin signaling affects Abeta pathology by regulating PS1 localization

Structural basis for the membrane association of ankyrinG via palmitoylation

Fujiwara, Y., Kondo, H., Shirota, M. et al. Structural basis for the membrane association of ankyrinG via palmitoylation. Sci Rep 6, 23981 (2016) doi:10.1038/srep2398

ATTED-II: a database of co-expressed genes and cis elements for identifying co-regulated gene groups in Arabidopsis

Publicly available database of co-expressed gene sets would be a valuable tool for a wide variety of experimental designs, including targeting of genes for functional identification or for regulatory investigation. Here, we report the construction of an Arabidopsis thaliana trans-factor and cis-element prediction database (ATTED-II) that provides co-regulated gene relationships based on co-expressed genes deduced from microarray data and the predicted cis elements. ATTED-II () includes the following features: (i) lists and networks of co-expressed genes calculated from 58 publicly available experimental series, which are composed of 1388 GeneChip data in A.thaliana; (ii) prediction of cis-regulatory elements in the 200 bp region upstream of the transcription start site to predict co-regulated genes amongst the co-expressed genes; and (iii) visual representation of expression patterns for individual genes. ATTED-II can thus help researchers to clarify the function and regulation of particular genes and gene networks