Biomedical subjects

Nobuhiro Go

Publications and source records attributed to Nobuhiro Go.

10 recordsLinked to original sources

PubMed2006

Amino acid residue doublet propensity in the protein-RNA interface and its application to RNA interface prediction.

Protein-RNA interactions play essential roles in a number of regulatory mechanisms for gene expression such as RNA splicing, transport, translation and post-transcriptional control. As the number of available protein-RNA complex 3D structures has increased, it is now possible to statistically examine protein-RNA interactions based on 3D structures. We performed computational analyses of 86 representative protein-RNA complexes retrieved from the Protein Data Bank. Interface residue propensity, a measure of the relative importance of different amino acid residues in the RNA interface, was calculated for each amino acid residue type (residue singlet interface propensity). In addition to the residue singlet propensity, we introduce a new residue-based propensity, which gives a measure of residue pairing preferences in the RNA interface of a protein (residue doublet interface propensity). The residue doublet interface propensity contains much more information than the sum of two singlet propensities alone. The prediction of the RNA interface using the two types of propensities plus a position-specific multiple sequence profile can achieve a specificity of about 80%. The prediction method was then applied to the 3D structure of two mRNA export factors, TAP (Mex67) and UAP56 (Sub2). The prediction enables us to point out candidate RNA interfaces, part of which are consistent with previous experimental studies and may contribute to elucidation of atomic mechanisms of mRNA export.

Amino Acids↗

PubMed2006

Switch interactions control energy frustration and multiple flagellar filament structures.

Bacterial flagellar filament is a macromolecular assembly consisting of a single protein, flagellin. Bacterial swimming is controlled by the conformational transitions of this filament between left- and right-handed supercoils induced by the flagellar motor torque. We present a massive molecular dynamics simulation that was successful in constructing the atomic-level supercoil structures consistent with various experimental data and further in elucidating the detailed underlying molecular mechanisms of the polymorphic supercoiling. We have found that the following three types of interactions are keys to understanding the supercoiling mechanism. "Permanent" interactions are always maintained between subunits in the various supercoil structures. "Sliding" interactions are formed between variable hydrophilic or hydrophobic residue pairs, allowing intersubunit shear without large change in energy. The formation and breakage of "switch" interactions stabilize inter- and intrasubunit interactions, respectively. We conclude that polymorphic supercoiling is due to the energy frustration between them. The transition between supercoils is achieved by a "transform and relax" mechanism: the filament structure is geometrically transformed rapidly and then slowly relaxes to energetically metastable states by rearranging interactions.

Computer Simulation↗

PubMed2005

Protein boson peak originated from hydration-related multiple minima energy landscape.

The boson peak is a broad peak found in the low-frequency region of inelastic neutron and Raman scattering spectra in many glassy materials, including biopolymers below approximately 200 K. Here, we give a novel insight into the origins of the protein boson peak, which may also be valid for materials other than proteins. Molecular simulation reveals that the structured water molecules around a protein molecule increase the number of local minima in the protein energy landscape, which plays a key role in the origin of the boson peak. The peak appears when the protein dynamics are trapped within a local energy minimum at cryogenic temperatures. This trapping causes very low frequency collective motions to shift to higher frequencies. We demonstrate that the characteristic frequency of such systems shifts higher as the temperature decreases also in model one-dimensional energy surfaces with multiple minima.

Animals↗

PubMed2005

Newly sequenced eRF1s from ciliates: the diversity of stop codon usage and the molecular surfaces that are important for stop codon interactions.

The genetic code of nuclear genes in some ciliates was found to differ from that of other organisms in the assignment of UGA, UAG, and UAA codons, which are normally assigned as stop codons. In some ciliate species, the universal stop codons UAA and UAG instead encode glutamine. In some other ciliates, the universal stop codon UGA appears to be translated as cysteine or tryptophan. Eukaryotic release factor 1 (eRF1) is a key protein in stop codon recognition, thus, the protein is believed to play an important role in the stop codon reassignment in ciliates. We have cloned, sequenced, and analyzed the cDNA of eRF1 from four ciliate species of three different classes: Karyorelictea (Loxodes striatus), Heterotrichea (Blepharisma musculus), and Litostomatea (Didinium nasutum, Dileptus margaritifer). Phylogenetic analysis of these eRF1s supports the hypothesis that the genetic code in ciliates has deviated independently several times from the universal genetic code, and that different ciliate eRF1s may have undergone different processes to change the codon specificity. Using computational methods, we have also suggested areas on the surface of eRF1s that are important for stop codon recognition in ciliate eRF1s.

Amino Acid Sequence↗

PubMed2004

Electrostatic potential of nucleotide-free protein is sufficient for discrimination between adenine and guanine-specific binding sites.

Despite sharing many common features, adenine-binding and guanine-binding sites in proteins often show a clear preference for the cognate over the non-cognate ligand. We have analyzed electrostatic potential (ESP) patterns at adenine and guanine-binding sites of a large number of non-redundant proteins where each binding site was first annotated as adenine/guanine-specific or non-specific from a survey of primary literature. We show that more than 90% of ESP variance at the binding sites is accounted for by only two principal component ESP vectors, each aligned to molecular dipoles of adenine and guanine. Projected on these principal component vectors, the adenine/guanine-specific and non-specific binding sites, including adenine-containing dinucleotides, show non-overlapping distributions. Adenine or guanine specificities of the binding sites also show high correlation with the corresponding electrostatic replacement (cognate by non-cognate ligand) energies. High correlation coefficients (0.94 for 35 adenine-binding sites and 1.0 for 20 guanine-binding sites) were obtained when adenine/guanine specificities were predicted using the replacement energies. Our results demonstrate that ligand-free protein ESP is an excellent indicator for discrimination between adenine and guanine-specific binding sites and that ESP of ligand-free protein can be used as a tool to annotate known and putative purine-binding sites in proteins as adenine or guanine-specific.

Adenine↗

PubMed2004

Filtering remote homologues using predicted structural information.

Finding homologues for a given protein plays a major role in predicting the protein's structure and function. However, it is still difficult to find remote homologues with low sequence similarity, even with advanced sequence search methods. We propose a simple filtering method that uses predicted structural information, pertaining to secondary structures and solvent accessibilities. It filters the more promising homologues from the many candidate proteins obtained by PSI-BLAST with a less stringent threshold E-value. The final decision is made by a simple linear discrimination method, considering the E-value of PSI-BLAST and the statistical significance scores of structural matches. An in-house neural network program is used for the prediction of secondary structures and solvent accessibilities for both the query and library proteins. The performance of our filtering method was evaluated by the cross-validation method, using the SCOP superfamily relationship as the correct standard. Coverage-reliability plots show that our filtering method clearly improves the performance of PSI-BLAST. The secondary structure improves PSI-BLAST better than the solvent accessibilities, but the combination of these two features with PSI-BLAST leads to the best result. The advantage of our method is its easy implementation with fewer parameters to be tuned and faster computation. We also discuss its performance with predicted and observed secondary structures.

Algorithms↗

PubMed2003

Novel types of two-domain multi-copper oxidases: possible missing links in the evolution.

An analysis of the genome sequence database revealed novel types of two-domain multi-copper oxidases. The two-domain proteins have the conspicuous combination of blue-copper and inter-domain trinuclear copper binding residues, which is common in ceruloplasmin and ascorbate oxidase but not in nitrite reductase, and therefore are considered to retain the characteristics of the plausible ancestral form of ceruloplasmin and ascorbate oxidase. A possible evolutionary relationship of these proteins is proposed.

Amino Acid Sequence↗

PubMed2003

Finding evolutionary relations beyond superfamilies: fold-based superfamilies.

Superfamily classifications are based variably on similarity of sequences, global folds, local structures, or functions. We have examined the possibility of defining superfamilies purely from the viewpoint of the global fold/function relationship. For this purpose, we first classified protein domains according to the beta-sheet topology. We then introduced the concept of kinship relations among the classified beta-sheet topology by assuming that the major elementary event leading to creation of a new beta-sheet topology is either an addition or deletion of one beta-strand at the edge of an existing beta-sheet during the molecular evolution. Based on this kinship relation, a network of protein domains was constructed so that the distance between a pair of domains represents the number of evolutionary events that lead one from the other domain. We then mapped on it all known domains with a specific core chemical function (here taken, as an example, that involving ATP or its analogs). Careful analyses revealed that the domains are found distributed on the network as >20 mutually disjointed clusters. The proteins in each cluster are defined to form a fold-based superfamily. The results indicate that >20 ATP-binding protein superfamilies have been invented independently in the process of molecular evolution, and the conservative evolutionary diffusion of global folds and functions is the origin of the relationship between them.

Adenosine Triphosphate↗

PubMed2002

Nonlinear temperature dependence of the crystal structure of lysozyme: correlation between coordinate shifts and thermal factors.

The static and dynamic structures of human lysozyme at seven different temperatures ranging from 113 to 178 K were investigated by normal-mode refinement of the cryogenic X-ray diffraction data collected from a single crystal. Normal-mode refinement decomposes the mean-square fluctuations of protein atoms from their average position into the contributions from the internal degrees of freedom, which change the shape of the protein structure, and those from the external degrees of freedom, which generate rigid-body motions in the crystal. While at temperatures below 150 K the temperature dependence of the total mean-square fluctuations shows a small gradient similar to that predicted theoretically by normal-mode analysis, at temperatures above 150 K there is an apparent inflection in the temperature dependence with a higher gradient. The inflection in the temperature dependence at temperatures above 150 K occurs mostly in the external degrees of freedom. Possible causes for the dynamic transition are discussed with respect to the crystal packing and physicochemical properties of crystalline water.

Crystallography, X-Ray↗

PubMedDate not supplied

Highly divergent actins from karyorelictean, heterotrich, and litostome ciliates.

We have cloned, sequenced, and characterized cDNA of actins from five ciliate species of three different classes of the phylum Ciliophora: Karyorelictea (Loxodes striatus), Heterotrichea (Blepharisma japonicum, Blepharisma musculus), and Litostomatea (Didinium nasutum, Dileptus margaritifer). Loxodes striatus uses UGA as the stop codon and has numerous in-frame UAA and UAG, which are translated into glutamine. The other four species use UAA as the stop codon and have no in-frame UAG nor UGA. The putative amino acid sequences of the newly determined actin genes were found to be highly divergent as expected from previous findings of other ciliate actins. These sequences were also highly divergent from other ciliate actins, indicating that actin genes are highly diverse even within the phylum Ciliophora. Phylogenetic analysis showed high evolutionary rate of ciliate actins. Our results suggest that the evolutionary rate was accelerated because of the differences in molecular interactions.

Actins↗