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At least 379 records · Page 21Linked to original sources
PubMed2000

Pulmonary surfactant protein B: a structural model and a functional analogue.

Surfactant proteins B and C (SP-B and SP-C), together with phospholipids, are important constituents of pulmonary surfactant and of preparations used for treatment of respiratory distress syndrome (RDS). SP-B belongs to the saposin family of homologous proteins, which include other lipid-interacting proteins, like the membranolytic NK-lysin. SP-B, in contrast to other saposins, is hydrophobic and a disulfide-linked dimer, and its mechanism of action is not known. A model of the three-dimensional structure of one SP-B subunit was generated from the structure of monomeric NK-lysin determined by nuclear magnetic resonance, and the SP-B dimer was formed by joining two subunits via the intersubunit disulfide bond Cys48-Cys48'. After energy minimization, intersubunit hydrogen bonds/ion pairs were formed between the strictly conserved residues Glu51 and Arg52, which creates a central non-polar region located in between two clusters of positively charged residues. The structural features support a function of SP-B in cross-linking of lipid membranes. Mixtures of phospholipids, an SP-C analogue and polymyxin B (which cross-links lipid vesicles but is structurally unrelated to SP-B) exhibit in vitro surface activity which is indistinguishable from that of analogous mixtures containing SP-B instead of polymyxin B. This suggests an avenue for identification of SP-B analogues that can be used in synthetic surfactants for treatment of RDS.

Amino Acid Sequence↗
PubMed1995

Sequence alignment and structural modelling of the LamB glycoporin family.

lamB gene segments were obtained from Yersinia enterocolitica and Vibrio parahaemolyticus by the PCR and the DNA sequence determined. The deduced polypeptide sequences showed high similarity to six other LamB-related proteins and all contained typical signature sequences present in all members of the family but not other proteins. The aligned amino acid sequences permitted derivation of a model of LamB folding across the bacterial outer membrane using an approach successfully applied in the identification of structural features in other porins (Ferenci,T. (1994) Mol. Microbiol. 14:188-189). The alignment-based model differs from previous LamB structure predictions and is also more complex than that found for OmpF-related porins; more than 16 conserved stretches of amino acid sequence potentially corresponded to membrane-spanning segments.

Amino Acid Sequence↗
PubMed1998

Static and dynamic finite element analyses of an idealized structural model of vertebral trabecular bone.

An idealized three-dimensional finite element model of a rodlike trabecular bone structure was developed to study its static and dynamic responses under compressive loading, considering the effects of bone marrow and apparent density. Static analysis of the model predicted hydraulic stiffening of trabecular bone due to the presence of bone marrow. The predicted power equation relating trabecular bone apparent elastic modulus to its apparent density was in good agreement with those of the reported experimental investigations. The ratio of the maximum stress in the trabecular bone tissue to its apparent stress had a high value, decreasing with increasing bone apparent density. Frequency analyses of the model predicted higher natural frequencies for the bone without marrow than those for the bone with marrow. Adding a mass relatively large compared to that of bone rendered a single-degree-of-freedom response. In this case, the resonant frequency was higher for the bone with marrow than that for the bone without marrow. The predicted vibrational measurement of apparent modulus was in good agreement with that of the static measurement, suggesting vibrational testing as a method for nondestructive measurement of trabecular bone elastic moduli.

Bone Density↗
PubMed2001

Structural models for the self-assembly and microtubule interactions of gamma-, delta- and epsilon-tubulin.

alphabeta-tubulin heterodimers self-assemble to form microtubules nucleated by gamma-tubulin in the cell. Gamma-tubulin is believed to recruit the alphabeta-tubulin dimers that form the minus ends of microtubules, but the molecular mechanism of this action remains a matter of heated controversy. Still less is known about the function and molecular interactions of delta-tubulin and epsilon-tubulin. delta-tubulin may seed the formation of the C triplet tubules in the basal bodies of Chlamydomonas and epsilon-tubulin is known to localize to the centrosome in a cell cycle-dependent manner. Using the structure of alphabeta tubulin as a model, we have analyzed the sequences of gamma-, delta- and epsilon-tubulin in regions corresponding to different polymerization interfaces in the tubulin alphabeta dimer. The sequence comparisons sometimes show clear conservation, pointing to similar types of contacts being functionally important for the new tubulin considered. Conversely, certain surfaces show marked differences that rule out equivalent interactions for non-microtubular tubulins. This sequence/structure analysis has led us to structural models of how these special tubulins may be involved in protein-protein contacts that affect microtubule self-assembly. delta-tubulin most likely interacts longitudinally with alpha-tubulin at the minus ends of microtubules, while epsilon-tubulin most likely binds to the plus end of beta-tubulin. Conservation of key residues in gamma-tubulin suggests that it is capable of longitudinal self-assembly. The implications for the protofilament and template models of nucleation are considered.

Amino Acid Sequence↗
PubMed2000

The bicyclomycin sensitivities of 38 bicyclomycin-resistant mutants of transcription termination protein rho and the location of their mutations support a structural model of rho based on the F(1) ATPase.

A total of 38 bicyclomycin-resistant mutants of Escherichia coli transcription termination protein Rho have been isolated. The locations of their mutations identify the ATP-binding region as the functional domain inhibited by bicyclomycin. Strains containing the S266C, S266A and L208R Rho mutations are very resistant to bicyclomycin in vivo. In a similar way, the mutant Rho proteins containing these mutations are very resistant to bicyclomycin in vitro. These data suggest that Ser266 and Leu208 might make direct contact with the antibiotic. These two residues are close to each other in the tertiary structure of a model of Rho based on the alpha and beta subunits of the F(1) ATPase, supporting the validity of the model. The strain containing the G337S Rho mutation also has high bicyclomycin resistance, and the proximity of L208, S266 and G337 in the quaternary structure of the Rho model has enabled a candidate bicyclomycin-binding pocket to be delineated. As a whole, the bicyclomycin sensitivities of the mutants are consistent with the locations of their respective mutations in the model of Rho based on the F(1) ATPase, therefore supporting the emerging consensus model of Rho structure.

Adenosine Triphosphate↗
PubMed1997

Meta-analyses of age-cognition relations in adulthood: estimates of linear and nonlinear age effects and structural models.

A meta-analysis was conducted on 91 studies to derive a correlation matrix for adult age, speed of processing, primary-working memory, episodic memory, reasoning, and spatial ability. Structural equation modeling with a single latent common cognitive factor showed that all cognitive measures shared substantial portions of age-related variance. A mediational model revealed that speed of processing and primary-working memory appear to be important mediators of age-related differences in the other measures. However, not all of the age-related influences were mediated. An examination of quadratic age effects and correlational patterns for subsamples under and over 50 years of age revealed that (a) negative age-cognition relations were significant for the 18- to 50-year-old sample and (b) the age-related decline accelerated significantly over the adult life span for variables assessing speed, reasoning, and episodic memory.

Adult↗
PubMed1987

A structural model for molded thermoplastic ankle-foot orthoses.

The structural response of a posterior leaf spring, ankle-foot orthosis (AFO) was studied both experimentally and with a simple theoretical model. The theoretical model, which was compared with other analytical solutions and experimental data, predicted the bending and twisting of the AFO due to unit loads. The simple theoretical model utilized beam equations and small deflection theory. Excellent agreement between test and predicted values was achieved, indicating that the simple theoretical model, which was relatively easy to implement computationally, could serve as the major component of a computer-aided design program.

Ankle↗
PubMed1995

The development of an age structured model for schistosomiasis transmission dynamics and control and its validation for Schistosoma mansoni.

Mathematical models are potentially useful tools to aid in the design of control programmes for parasitic diseases. In this paper, a fully age structured epidemiological model of human schistosomiasis is developed and parameterized, and used to predict trends in infection prevalence, intensity and prevalence of heavy infections over age and time during several rounds of mass and age targeted treatment. The model is validated against data from a Schistosoma mansoni control programme in Kenya.

Adolescent↗
PubMed1998

Structural modeling of the complex between an acetylcholine receptor-mimicking antibody and its snake toxin antigen.

The antibody M alpha2-3 neutralizes the functional, acetylcholine receptor binding activity of its antigen, neurotoxin alpha, and exhibits several other properties in common with the receptor itself. We present here the results of calculations examining the three-dimensional structure of the toxin alpha:M alpha2-3 complex. The antigen structure, determined by nuclear magnetic resonance spectroscopy, was docked to models of the variable fragment of the antibody combining site by using a method based on surface complementarity and maximization of buried surface area while taking into account the possibility of conformational change on complexation. Extensive experimental information on the location of the functional epitope was incorporated into the analysis and used to screen candidate geometries of the complex resulting from the modeling. Eight plausible structures that are in accord with the experimental data were derived. Common structural features of the models are discussed, and residues of the antibody-combining site that are expected to play important roles in complexation are identified. In particular, three epitope residues that, according to mutagenesis experiments, make particularly strong contributions to the binding, interact excentrically and do not make contact with the central loops of the combining site, L3 and H3.

Animals↗
PubMed1985

Structural model for the trialkyltin binding site on cat hemoglobin.

The binding site for trialkyltin complexes on the alpha- chain of cat oxyhemoglobins is proposed to involve the SG and NE2 atoms of Cys-13 and His-113 respectively. On deoxygenation, the conformation of this region changes substantially, allowing complexation only through the ND1 nitrogen atom of His-113, a much less favorable interaction. Thus the model presented explains the preferential binding of trialkyltin complexes to R-state cat hemoglobin and suggests the type of interaction that is likely to occur between these compounds and a variety of less well-characterized enzymes to produce the metabolic effects that trialkyltin complexes are known to produce in vivo.

Animals↗
PubMed1998

Structural model of the HIV-1 Tat(46-58)-TAR complex.

The trans-activator protein (Tat) of human immunodeficiency virus type 1 (HIV-1) binds to an uridine-rich bulge of an RNA target (TAR; trans-activation responsive element) predominantly via its basic sequence domain. The structure of the Tat(46-58)-TAR complex has been determined by a novel modeling approach relying on structural information about one crucial arginine residue and crosslink data. The strategy described here solely uses this experimental data without additional "modeling" assumptions about the structure of the complex in order to avoid human bias. Model building was performed in a fashion similar to structure calculations from nuclear magnetic resonance (NMR)-spectroscopic data using restrained molecular dynamics. The resulting set of structures of Tat(46-58) in its complex with TAR reveals that all models have converged to a common fold, showing a backbone root mean square deviation (RMSD) of 1.36A. Analysis of the calculated structures suggests that HIV-I Tat forms a hairpin loop in its complex with TAR that shares striking similarity to the hairpin formed by the structure of the bovine immunodeficiency virus Tat protein after TAR binding as determined by NMR studies. The outlined approach is not limited to the Tat-TAR complex modeling, but is also applicable to all molecular complexes with sufficient biochemical and biophysical data available.

Amino Acid Sequence↗
PubMed1995

Structural model of the phospholamban ion channel complex in phospholipid membranes.

Phospholamban is a 52 amino acid residue membrane protein involved with the regulation of calcium levels across sarcoplasmic reticulum membranes in cardiac muscle cells. The N-terminal 30 amino acid residues of the protein are largely hydrophilic and include two sites whose phosphorylation is thought to dissociate an inhibitory complex between phospholamban and Ca2+ ATPase. The C-terminal 22 amino acid residues are largely hydrophobic, anchor the protein in the membrane and are responsible for Ca2+ selective ion conductance. Specific interactions between the transmembrane domains stabilize a pentameric protein complex. We have obtained circular dichroism (CD), transmission Fourier transform infrared (FTIR) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectra of the full-length protein and have compared these results to those from a 28 residue peptide that includes the transmembrane domain. Both proteins reconstituted into phospholipid membranes are largely alpha-helical by CD and FTIR. Polarized ATR-FTIR measurements show that both the cytosolic and transmembrane helices are oriented perpendicular to the membrane plane with a tilt of 28 (+/- 6) degrees with respect to the membrane normal. This tilt angle is in close agreement to that calculated from a model for the transmembrane domain of phospholamban suggested by mutagenesis and molecular modeling. Phosphorylation does not significantly change the secondary structure or orientation of the protein. The pentameric complex is modeled as a left-handed coiled-coil of five long helices (40 (+/- 3) residues) that extend across the membrane from the lumenal carboxy terminus to the phosphorylation site in the cytoplasm. The helix bundle forms a perpendicular ion pore that may begin at a distance (17 to 29 A) from the membrane surface. Based on the above, we propose a mechanism by which phospholamban regulates Ca2+ levels across membranes that takes into account both its selective ion conductance and inhibitory association with the Ca2+ pump.

Amino Acid Sequence↗
PubMed1987

Proton NMR studies of the biologically active 1-34 fragment of bovine parathyroid hormone: examination of a structural model.

Proton NMR spectra of the biologically active 1-34 fragment of bovine parathyroid hormone (bPTH) were studied as a function of pH over the range of pH 4 to 10, in buffer and in 6 M guanidine DC1. One of the histidine C-2 peaks titrated normally, with a pKa value of 6.8, but the other two histidines in this peptide had pKa values of 6.3. Denatured PTH showed only one histidine C-2 peak with a pKa of 6.7. An aliphatic peak identified as due to either a methionine or a glutamine residue also shifted with pH, and the pKa for this shift was 6.3. Finally, small but significant upfield shifts in the methyl and methylene resonances were observed as a function of pH, and when compared to the denatured peptide. These results indicate that the N-terminal domain of native PTH has considerable structure in solution, and are consistent with a theoretical model for the folding of this peptide.

Animals↗
PubMed1989

Envelope structure model of human immunodeficiency virus type 1.

The envelope structure of human immunodeficiency virus type 1 (HIV-1) was examined using a computer image processor combined with an image rotation-averaging system. Our results indicate that the envelope of the HIV-1 particle is constructed of a T-7 laevo icosahedral surface net, and the knobs are distributed in the positions of pentamer-hexamer clustering, the total number being 72, which correspond to the results obtained by Gelderblom et al. and Ozel et al.

HIV-1↗
PubMed1991

A structured model for vegetative growth and sporulation in Bacillus thuringiensis.

A mathematical model has been developed for the delta-endotoxin producing Bacillus thuringiensis. The structure of the model involves the processes taking place during vegetative growth, those leading to the initiation of sporulation under conditions of carbon and/or nitrogen limitation, and the sporulation events. The key features in the model are the pools of compounds, such as PRPP, IMP, ADP/ATP, GDP/GTP, pyrimidine nucleotides, NAD/NADH2, amino acids, nucleic acids, cell wall, and vegetative and sporulation proteins. These, along with sigma-factors that control the nature of RNA-polymerase during the different phases, effectively stimulate the vegetative growth and sporulation. The initiation of sporulation is controlled by the intracellular concentration of GTP. Results of simulation of vegetative growth, initiation of sporulation, spore protein formation, and production of delta-endotoxin under C- or N-limitation are presented.

Ammonia↗
PubMed2001

Binaural processing model based on contralateral inhibition. I. Model structure.

This article presents a quantitative binaural signal detection model which extends the monaural model described by Dau et al. [J. Acoust. Soc. Am. 99, 3615-3622 (1996)]. The model is divided into three stages. The first stage comprises peripheral preprocessing in the right and left monaural channels. The second stage is a binaural processor which produces a time-dependent internal representation of the binaurally presented stimuli. This stage is based on the Jeffress delay line extended with tapped attenuator lines. Through this extension, the internal representation codes both interaural time and intensity differences. In contrast to most present-day models, which are based on excitatory-excitatory interaction, the binaural interaction in the present model is based on contralateral inhibition of ipsilateral signals. The last stage, a central processor, extracts a decision variable that can be used to detect the presence of a signal in a detection task, but could also derive information about the position and the compactness of a sound source. In two accompanying articles, the model predictions are compared with data obtained with human observers in a great variety of experimental conditions.

Attention↗