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At least 235 records · Page 13Linked to original sources

PubMed2006

Novel hybrid method for the evaluation of parameters contributing in determination of protein structural classes.

Due to the increasing gap between structure-determined and sequenced proteins, prediction of protein structural classes has been an important problem. It is very important to use efficient sequential parameters for developing class predictors because of the close sequence-structure relationship. The multinomial logistic regression model was used for the first time to evaluate the contribution of sequence parameters in determining the protein structural class. An in-house program generated parameters including single amino acid and all dipeptide composition frequencies. Then, the most effective parameters were selected by a multinomial logistic regression. Selected variables in the multinomial logistic model were Valine among single amino acid composition frequencies and Ala-Gly, Cys-Arg, Asp-Cys, Glu-Tyr, Gly-Glu, His-Tyr, Lys-Lys, Leu-Asp, Leu-Arg, Pro-Cys, Gln-Met, Gln-Thr, Ser-Trp, Val-Asn and Trp-Asn among dipeptide composition frequencies. Also a neural network model was constructed and fed by the parameters selected by multinomial logistic regression to build a hybrid predictor. In this study, self-consistency and jackknife tests on a database constructed by Zhou [1998. An intriguing controversy over protein structural class prediction. J. Protein Chem. 17(8), 729-738] containing 498 proteins are used to verify the performance of this hybrid method, and are compared with some of prior works. The results showed that our two-stage hybrid model approach is very promising and may play a complementary role to the existing powerful approaches.

Amino Acid Sequence↗

PubMed1983

Occluded and Budded Autographa californica Nuclear Polyhedrosis Virus: Immunological Relatedness of Structural Proteins.

The immunological relatedness of the structural proteins of the budded and occluded phenotypes of Autographa californica nuclear polyhedrosis virus was examined by reciprocal immunoblotting and by in situ peroxidase-antiperoxidase staining of virus-induced cell surface and intracellular antigens with antisera to both phenotypes. The molecular weights (MWs) of major structural proteins of both phenotypes that reciprocally cross-reacted were 92,500, 78,000, 62,500, 54,000, and 42,000. A highly immunogenic, major structural protein of the occluded phenotype of 46,000 MW was not recognized by antiserum to the budded phenotype, and a major structural protein of the budded phenotype, 48,000 MW, was not recognized by antiserum to the occluded phenotype. Both the budded and occluded phenotypes contained a protein of 33,500 MW that comigrated with polyhedrin (the matrix protein) and reacted with antiserum and monoclonal antibody to polyhedrin. Evidence was obtained for the apparent antigenic relatedness of proteins of different MWs from the budded and occluded phenotypes, possibly indicative of different processing of some proteins for the two phenotypes. Antiserum to the occluded phenotype recognized virus-induced cell surface antigens, indicating antigenic similarities between the occluded phenotype and envelope proteins of the budded phenotype. Antiserum to the budded phenotype recognized viral proteins produced before the appearance of cytopathic effect, whereas antiserum to the occluded phenotype did not.

Journal Article↗

PubMed2003

Robert Feulgen Lecture. Microscopic assessment of membrane protein structure and function.

Membrane proteins represent an important class of proteins that are encoded by about 40% of all genes, but compared to soluble proteins structural information is sparse. Most of the atomic coordinates currently available are from bacterial membrane proteins and have been obtained by X-ray crystallography. Recent results demonstrate the imaging power of the atomic force microscope and the accuracy of electron crystallography. These methods allow membrane proteins to be studied while embedded in the bilayer, and thus in a functional state. The low signal-to-noise ratio of cryoelectron microscopy is overcome by crystallizing membrane proteins in a two-dimensional protein-lipid membrane, allowing its atomic structure to be determined. In contrast, the high signal-to-noise ratio of atomic force microscopy allows individual protein surfaces to be imaged at subnanometer resolution, and their conformational states to be sampled. This review discusses examples of microscopic membrane protein structure determination and illuminates recent progress.

Animals↗

PubMed2004

Refinement of homology-based protein structures by molecular dynamics simulation techniques.

The use of classical molecular dynamics simulations, performed in explicit water, for the refinement of structural models of proteins generated ab initio or based on homology has been investigated. The study involved a test set of 15 proteins that were previously used by Baker and coworkers to assess the efficiency of the ROSETTA method for ab initio protein structure prediction. For each protein, four models generated using the ROSETTA procedure were simulated for periods of between 5 and 400 nsec in explicit solvent, under identical conditions. In addition, the experimentally determined structure and the experimentally derived structure in which the side chains of all residues had been deleted and then regenerated using the WHATIF program were simulated and used as controls. A significant improvement in the deviation of the model structures from the experimentally determined structures was observed in several cases. In addition, it was found that in certain cases in which the experimental structure deviated rapidly from the initial structure in the simulations, indicating internal strain, the structures were more stable after regenerating the side-chain positions. Overall, the results indicate that molecular dynamics simulations on a tens to hundreds of nanoseconds time scale are useful for the refinement of homology or ab initio models of small to medium-size proteins.

Algorithms↗

PubMed2026

Uncovering viral protein acquisition events and human-specific folds with pairwise comparisons of predicted protein structures.

Pairwise sequence comparisons are at the center of molecular evolutionary analyses. However, viral pairwise comparisons are challenging because extreme mutation rates and evolutionary pressure cause genomes to diverge rapidly, limiting detectable sequence similarity to fewer than 3% of virus pairs. To overcome these limitations, we compared viruses based on structural similarity, using predicted protein structures from ColabFold and Foldseek to define protein fold clusters. We represented each virus genome by its protein structural content. Pairwise similarities between viruses were then quantified using the Jaccard index based on the presence or absence of protein fold clusters. Using a recently established viral protein fold database, we compared all pairs of eukaryotic viruses in RefSeq. This approach increased the proportion of comparable viral genome pairs from 2.4% to 16.5%. Using this protein-fold representation of viruses, we were able to accurately predict viral families with an average sensitivity of 85.9%. Investigation of viral families showing limited sensitivity with this approach uncovered a laterally transferred structural cluster (Rep/NS1) broadly shared across diverse viral families and found in the avian lineage of adenoviruses. Sequence homology suggests that this Rep was acquired from Parvoviridae, but the protein is mutant in the ATPase active site, indicating possible exaptation toward a purely DNA-binding function. In Gammapapillomaviruses, several E4 clusters were associated with human tropism. In summary, by representing viruses with structural protein clusters, we can classify highly divergent viruses, trace lateral gene transfer, and uncover features associated with viral host range.

Humans↗

PubMed2006

Protein structure comparison: implications for the nature of 'fold space', and structure and function prediction.

The identification of geometric relationships between protein structures offers a powerful approach to predicting the structure and function of proteins. Methods to detect such relationships range from human pattern recognition to a variety of mathematical algorithms. A number of schemes for the classification of protein structure have found widespread use and these implicitly assume the organization of protein structure space into discrete categories. Recently, an alternative view has emerged in which protein fold space is seen as continuous and multidimensional. Significant relationships have been observed between proteins that belong to what have been termed different 'folds'. There has been progress in the use of these relationships in the prediction of protein structure and function.

Computational Biology↗

PubMed1993

Protein structure comparison by alignment of distance matrices.

With a rapidly growing pool of known tertiary structures, the importance of protein structure comparison parallels that of sequence alignment. We have developed a novel algorithm (DALI) for optimal pairwise alignment of protein structures. The three-dimensional co-ordinates of each protein are used to calculate residue-residue (C alpha-C alpha) distance matrices. The distance matrices are first decomposed into elementary contact patterns, e.g. hexapeptide-hexapeptide submatrices. Then, similar contact patterns in the two matrices are paired and combined into larger consistent sets of pairs. A Monte Carlo procedure is used to optimize a similarity score defined in terms of equivalent intramolecular distances. Several alignments are optimized in parallel, leading to simultaneous detection of the best, second-best and so on solutions. The method allows sequence gaps of any length, reversal of chain direction and free topological connectivity of aligned segments. Sequential connectivity can be imposed as an option. The method is fully automatic and identifies structural resemblances and common structural cores accurately and sensitively, even in the presence of geometrical distortions. An all-against-all alignment of over 200 representative protein structures results in an objective classification of known three-dimensional folds in agreement with visual classifications. Unexpected topological similarities of biological interest have been detected, e.g. between the bacterial toxin colicin A and globins, and between the eukaryotic POU-specific DNA-binding domain and the bacterial lambda repressor.

Actins↗

PubMed1992

Intracellular transport of rubella virus structural proteins expressed from cloned cDNA.

The structural proteins of rubella virus consist of a nucleocapsid protein (C) and two membrane-embedded spike glycoproteins (E1 and E2). Since many reports have suggested that rubella virus buds intracellularly, we have examined the intracellular transport of the structural proteins in the absence of virion formation, particularly whether the membrane glycoproteins are retained inside the cell or are transported to the cell surface. We have expressed the structural proteins from cloned cDNA either alone or in different combinations, have examined the intracellular location of the proteins by immunofluorescence and using biochemical methods, and have looked for plasma membrane-localized E1 or E2 using a cell surface biotinylation assay. The C protein was found in the Golgi complex when expressed with E2 and E1; without the membrane glycoproteins, C appeared to remain in the endoplasmic reticulum (ER). When expressed alone, E1 was retained in a pre-Golgi compartment, and was not detected at the cell surface in any cell line. When E2 was expressed alone a small fraction could be detected at the cell surface, but the majority was retained intracellularly, apparently in the ER and the Golgi. Both proteins were transported to the surface when they were expressed together, albeit with low efficiencies in all cell lines. These data suggest that, although neither glycoprotein carries a dominant intracellular retention signal, E2 and E1 are largely retained in the Golgi even when present as a transport-competent heterodimer.

Amino Acid Sequence↗

PubMed1996

Relationship between protein structure and geometrical constraints.

We evaluate to what extent the structure of proteins can be deduced from incomplete knowledge of disulfide bridges, surface assignments, secondary structure assignments, and additional distance constraints. A cost function taking such constraints into account was used to obtain protein structures using a simple minimization algorithm. For small proteins, the approximate structure could be obtained using one additional distance constraint for each amino acid in the protein. We also studied the effect of using predicted secondary structure and surface assignments. The constraints used in this approach typically may be obtained from low-resolution experimental data. When using a cost function based on distances, half of the resulting structures will be mirrored, because the resulting structure and its mirror image will have the same cost. The secondary structure assignments were therefore divided into chirality constraints and distance constraints. Here we report that the problem of mirrored structures, in some cases, can be solved by using a chirality term in the cost function.

Protein Structure, Secondary↗

PubMed1991

High level expression of the major core protein VP7 and the non-structural protein NS3 of bluetongue virus in yeast: use of expressed VP7 as a diagnostic, group-reactive antigen in a blocking ELISA.

The major core protein VP7 and a non-structural protein NS3 of bluetongue virus serotype 1 have been synthesized from recombinant plasmids using both an in vitro transcription/translation system and a yeast expression system. Bluetongue virus genes were transcribed under the control of the bacteriophage SP6 promoter and the regulatable yeast metallothionein promoter. An indirect ELISA showed that expression of NS3 in yeast was inducible with 1 mM CuSO4 and VP7 synthesis was constitutive but could be further induced. The preferred procedure for antigen extraction from yeast was sonication for VP7 and SDS/NaOH treatment for NS3. Yeast-expressed VP7 antigen and a monoclonal antibody were used in a blocking ELISA to distinguish sera raised against bluetongue virus serotypes from those generated to viruses of the epizootic haemorrhagic disease serogroup.

Antigens, Viral↗

PubMed1993

Progress in protein structure prediction?

Prediction of protein secondary structure is an old problem and progress has been slow. Recently, spectacular success has been claimed in the blind prediction of the catalytic subunit of the cAMP-dependent protein kinase. When predictions in this and other test cases are assessed critically, some claims of prediction success turn out to be exaggerated, but a kernel of real progress remains: protein structure prediction can be improved substantially when a family of related sequences is available. Enough so that molecular biologists equipped with a new amino acid sequence and a multiple sequence alignment in hand may be tempted to test the new prediction methods.

Amino Acid Sequence↗

PubMed2005

Comparative modelling of protein structure and its impact on microbial cell factories.

Comparative modeling is becoming an increasingly helpful technique in microbial cell factories as the knowledge of the three-dimensional structure of a protein would be an invaluable aid to solve problems on protein production. For this reason, an introduction to comparative modeling is presented, with special emphasis on the basic concepts, opportunities and challenges of protein structure prediction. This review is intended to serve as a guide for the biologist who has no special expertise and who is not involved in the determination of protein structure. Selected applications of comparative modeling in microbial cell factories are outlined, and the role of microbial cell factories in the structural genomics initiative is discussed.

Journal Article↗

PubMed2005

Use of infrared spectroscopy to monitor protein structure and stability.

One of the most versatile methods for monitoring the structure of proteins, either in solution or in the solid state, is Fourier transform infrared spectroscopy. Also known as mid-range infrared, which covers the frequency range from 4000 to 400 cm(-1), this wavelength region includes bands that arise from three conformationally sensitive vibrations within the peptide backbone (amide I, II and III). Of these vibrations, amide I is the most widely used and can provide information on secondary structure composition and structural stability. One of the advantages of infrared spectroscopy is that it can be used with proteins that are either in solution or in the solid state. The use of infrared to monitor protein structure and stability is summarized herein. In addition, specialized infrared methods are presented, such as techniques for the study of membrane proteins and oriented samples. In addition, there is a growing body of literature on the use of infrared to follow reaction kinetics and ligand binding in proteins, as well as a number of infrared studies on protein dynamics. Finally, the potential for using near-infrared spectroscopy to study protein structure is introduced.

Animals↗

PubMed2006

Sequence-based protein structure prediction using a reduced state-space hidden Markov model.

This work describes the use of a hidden Markov model (HMM), with a reduced number of states, which simultaneously learns amino acid sequence and secondary structure for proteins of known three-dimensional structure and it is used for two tasks: protein class prediction and fold recognition. The Protein Data Bank and the annotation of the SCOP database are used for training and evaluation of the proposed HMM for a number of protein classes and folds. Results demonstrate that the reduced state-space HMM performs equivalently, or even better in some cases, on classifying proteins than a HMM trained with the amino acid sequence. The major advantage of the proposed approach is that a small number of states is employed and the training algorithm is of low complexity and thus relatively fast.

Algorithms↗

PubMed1996

Proteins encoded by open reading frames 3 and 4 of the genome of Lelystad virus (Arteriviridae) are structural proteins of the virion.

Four structural proteins of Lelystad virus (Arteriviridae) were recognized by monoclonal antibodies in a Western immunoblotting experiment with purified virus. In addition to the 18-kDa integral membrane protein M and the 15-kDa nucleocapsid protein N, two new structural proteins with molecular masses of 45 to 50 kDa and 31 to 35 kDa, respectively, were detected. Monoclonal antibodies that recognized proteins of 45 to 50 kDa and 31 to 35 kDa immunoprecipitated similar proteins expressed from open reading frames (ORFs) 3 and 4 in baculovirus recombinants, respectively. Therefore, the 45- to 50-kDa protein is encoded by ORF3 and the 31- to 35-kDa protein is encoded by ORF4. Peptide-N-glycosidase F digestion of purified virus reduced the 45- to 50-kDa and 31- to 35-kDa proteins to core proteins of 29 and 16 kDa, respectively, which indicates N glycosylation of these proteins in the virion. Monoclonal antibodies specific for the 31- to 35-kDa protein neutralized Lelystad virus, which indicates that at least part of this protein is exposed at the virion surface. We propose that the 45- to 50-kDa and 31- to 35-kDa structural proteins of Lelystad virus be named GP3 and GP4, to reflect their glycosylation and the ORFs from which they are expressed. Antibodies specific for GP3 and GP4 were detected by a Western immunoblotting assay in swine serum after an infection with Lelystad virus.

Amidohydrolases↗

PubMed2003

GeneSilico protein structure prediction meta-server.

Rigorous assessments of protein structure prediction have demonstrated that fold recognition methods can identify remote similarities between proteins when standard sequence search methods fail. It has been shown that the accuracy of predictions is improved when refined multiple sequence alignments are used instead of single sequences and if different methods are combined to generate a consensus model. There are several meta-servers available that integrate protein structure predictions performed by various methods, but they do not allow for submission of user-defined multiple sequence alignments and they seldom offer confidentiality of the results. We developed a novel WWW gateway for protein structure prediction, which combines the useful features of other meta-servers available, but with much greater flexibility of the input. The user may submit an amino acid sequence or a multiple sequence alignment to a set of methods for primary, secondary and tertiary structure prediction. Fold-recognition results (target-template alignments) are converted into full-atom 3D models and the quality of these models is uniformly assessed. A consensus between different FR methods is also inferred. The results are conveniently presented on-line on a single web page over a secure, password-protected connection. The GeneSilico protein structure prediction meta-server is freely available for academic users at http://genesilico.pl/meta.

Internet↗

PubMed2001

The RESID Database of protein structure modifications and the NRL-3D Sequence-Structure Database.

The RESID Database is a comprehensive collection of annotations and structures for protein post-translational modifications including N-terminal, C-terminal and peptide chain cross-link modifications. The RESID Database includes systematic and frequently observed alternate names, Chemical Abstracts Service registry numbers, atomic formulas and weights, enzyme activities, taxonomic range, keywords, literature citations with database cross-references, structural diagrams and molecular models. The NRL-3D Sequence-Structure Database is derived from the three-dimensional structure of proteins deposited with the Research Collaboratory for Structural Bioinformatics Protein Data Bank. The NRL-3D Database includes standardized and frequently observed alternate names, sources, keywords, literature citations, experimental conditions and searchable sequences from model coordinates. These databases are freely accessible through the National Cancer Institute-Frederick Advanced Biomedical Computing Center at these web sites: http://www. ncifcrf.gov/RESID, http://www.ncifcrf.gov/NRL-3D; or at these National Biomedical Research Foundation Protein Information Resource web sites: http://pir.georgetown.edu/pirwww/dbinfo/resid .html, http://pir.georgetown.edu/pirwww/dbinfo/nrl3d .html

Amino Acids↗

PubMed2000

Identification and characterization of a structural protein of hepatitis B virus: a polymerase and surface fusion protein encoded by a spliced RNA.

The hepatitis B virus (HBV) genome is known to contain four conserved and overlapped open reading frames (ORFs) encoding the viral core, polymerase (P), surface (S), and X proteins. Whether HBV encodes other proteins has long been a major interest in the field. Using (32)P-labeling of an introduced protein kinase A site attached to the N- or C-terminus of the HBV polymerase gene, a 43-kDa P-S fusion protein was detected in cell lysate, secreted virions, and 22-nm subviral particles. Immunobiochemical studies showed that the 43-kDa protein contains the epitopes of the N-terminus of polymerase and most parts of the surface proteins. This 43-kDa protein was shown to be a glycoprotein, similar to the surface protein. RT-PCR and sequence analyses identified a spliced mRNA which was derived from pregenomic RNA with a deletion of 454 nucleotides (nt) from nt 2447 to 2902. This splice event creates a P-S fusion ORF. This finding is consistent with the result obtained from an immunobiochemical study. Mutations at the splice donor or acceptor site on the HBV genome abrogated the production of the 43-kDa protein. These mutants had no effect on viral replication in transfected HuH-7 cells. However, this P-S fusion protein is able to substitute for the LS protein in virion maturation. On the basis of these results, we conclude that the 43-kDa protein is a polymerase-surface fusion protein encoded by a spliced RNA. Similar to the LS protein, the 43-kDa P-S fusion protein is a structural protein of HBV and might play a role in the HBV life cycle.

Aspartic Acid Endopeptidases↗