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Results for “protein function”

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PubMed1996

Construction and expression of bi-functional proteins of single-chain Fv with effector domains.

We fused various polypeptide extensions to the C-termini of single chain Fv (scFv) and disulfide-stabilized Fv (dsFv) fragments to facilitate detection of bi-functional proteins or to add biological effector domains, which included the human metallothionein (HMT) motif and biotin mimetic sequence. These bi-functional proteins were expressed and secreted in a recombinant Pichia pastoris system and showed specific anti-idiotype binding activity, as determined by competitive radioimmunoassaying. However, the fusion protein constructed with dsFv- HMT, but not scFv-HMT, had lost this binding activity. The interruption of the structural conformation as a result in dsFv-HMT may be explained by the interactions between the cysteines engineered in dsFv domains and the cysteines in the HMT region.

Amino Acid Sequence↗

PubMed2001

Tyrosine nitration: localisation, quantification, consequences for protein function and signal transduction.

The nitration of free tyrosine or protein tyrosine residues generates 3-nitrotyrosine the detection of which has been utilised as a footprint for the in vivo formation of peroxynitrite and other reactive nitrogen species. The detection of 3-nitrotyrosine by analytical and immunological techniques has established that tyrosine nitration occurs under physiological conditions and levels increase in most disease states. This review provides an updated, comprehensive and detailed summary of the tissue, cellular and specific protein localisation of 3-nitrotyrosine and its quantification. The potential consequences of nitration to protein function and the pathogenesis of disease are also examined together with the possible effects of protein nitration on signal transduction pathways and on the metabolism of proteins.

Animals↗

PubMed1998

Mechanisms of Bcl-2 protein function.

The Bcl-2 protein blocks a distal step in an evolutionarily conserved pathway for programmed cell death and apoptosis. The gene encoding this protein was first discovered because of its involvement in the t(14;18) chromosomal translocations commonly found in B-cell lymphomas. Overexpression of Bcl-2 also occurs in many other types of human cancers, and prevents cell death induced by nearly all anticancer drugs and radiation. Since the discovery of Bcl-2 over ten years ago, several cellular and viral homologs have been identified, some of which suppress cell death and others which promote apoptosis. Many of these proteins can interact with each other through a complex network of homo- and heterodimers. Though functionally important, dimerization events still do not explain in a broader sense how these proteins actually control cell life and death. Recent findings that Bcl-2 can function both as an ion channel and as an adapter or docking protein however are beginning to provide insights into the molecular mechanisms through which these proteins regulate the programmed cell death pathway in normalcy and disease.

Animals↗

PubMed2005

Inhibited cell growth and protein functional changes from an editing-defective tRNA synthetase.

The genetic code is established in aminoacylation reactions catalyzed by aminoacyl-tRNA synthetases. Many aminoacyl-tRNA synthetases require an additional domain for editing, to correct errors made by the catalytic domain. A nonfunctional editing domain results in an ambiguous genetic code, where a single codon is not translated as a specific amino acid but rather as a statistical distribution of amino acids. Here, wide-ranging consequences of genetic code ambiguity in Escherichia coli were investigated with an editing-defective isoleucyl-tRNA synthetase. Ambiguity retarded cell growth at most temperatures in rich and minimal media. These growth rate differences were seen regardless of the carbon source. Inclusion of an amino acid analogue that is misactivated (and not cleared) diminished growth rate by up to 100-fold relative to an isogenic strain with normal editing function. Experiments with target-specific antibiotics for ribosomes, DNA replication, and cell wall biosynthesis, in conjunction with measurements of mutation frequencies, were consistent with global changes in protein function caused by errors of translation and not editing-induced mutational errors. Thus, a single defective editing domain caused translationally generated global effects on protein functions that, in turn, provide powerful selective pressures for maintenance of editing by aminoacyl-tRNA synthetases.

Amino Acyl-tRNA Synthetases↗

PubMed2005

Mining protein function from text using term-based support vector machines.

BACKGROUND: Text mining has spurred huge interest in the domain of biology. The goal of the BioCreAtIvE exercise was to evaluate the performance of current text mining systems. We participated in Task 2, which addressed assigning Gene Ontology terms to human proteins and selecting relevant evidence from full-text documents. We approached it as a modified form of the document classification task. We used a supervised machine-learning approach (based on support vector machines) to assign protein function and select passages that support the assignments. As classification features, we used a protein's co-occurring terms that were automatically extracted from documents. RESULTS: The results evaluated by curators were modest, and quite variable for different problems: in many cases we have relatively good assignment of GO terms to proteins, but the selected supporting text was typically non-relevant (precision spanning from 3% to 50%). The method appears to work best when a substantial set of relevant documents is obtained, while it works poorly on single documents and/or short passages. The initial results suggest that our approach can also mine annotations from text even when an explicit statement relating a protein to a GO term is absent. CONCLUSION: A machine learning approach to mining protein function predictions from text can yield good performance only if sufficient training data is available, and significant amount of supporting data is used for prediction. The most promising results are for combined document retrieval and GO term assignment, which calls for the integration of methods developed in BioCreAtIvE Task 1 and Task 2.

Computational Biology↗

PubMed2002

Modulation of globular protein functionality by weakly interacting cosolvents.

Globular proteins are utilized in food, pharmaceutical, and health-care products because of their unique functional attributes, for example, enzyme catalysis, ligand binding and transport, surface activity and self-association. The expression of these functional attributes in a particular product depends on the molecular structure, chemical environment and thermal-mechanical history of the proteins. The optimization of the design and operation of processing technologies used to manufacture protein-containing materials depends on a thorough understanding of the influence of processing conditions and material composition on protein properties. This paper focuses on the impact of weakly interacting neutral cosolvents (such as sugars and polyols) on the structural, thermodynamic and functional properties of globular proteins in foods. The physicochemical mechanisms by which these cosolvents can modulate protein functionality are highlighted, that is, differential interactions and steric exclusion. Previous studies of the impact of cosolvents on protein functionality that are relevant to foods are reviewed, for example, water solubility, stabilization, emulsification, foaming, gelation, enzyme catalysis, and flavor binding.

Dietary Proteins↗

PubMed2006

Recent advances in clarifying prion protein functions using knockout mice and derived cell lines.

Considerable information on the functions of prion protein (PrP) has been accumulated. One experimental approach is the use of PrP gene-knockout mice and derived cell lines. This approach has contributed to elucidating the functions of cellular prion protein (PrP(C)), such as its anti-oxidative and anti-apoptotic roles. This review will introduce the recent advances in prion biology made possible by the availability of these tools.

Animals↗

PubMed2003

Identification of transmembrane protein functions by binary topology patterns.

We propose a novel method for identifying and classifying the functions of transmembrane (TM) proteins based on their TM topology [the number of TM segments (tms), the loop length and the N-terminus location]. In this method, the TM topology is expressed as a string of '0' and '1', and this is designated the binary topology pattern (BTP). We focused on TM proteins with up to 12 tms, with the exception of 1 and 9 tms, and classified them into 37 functional groups by the number of tms and the functional annotation. These grouped TM protein sequences were used to determine BTPs which are specific to the individual functional groups. Since the evaluated accuracies (sensitivity, specificity and self-consistency) of these patterns in functional identification were quite high overall, i.e. 0.940, 0.934 and 0.935, respectively, as averaged over the 37 functional groups, we confirmed that TM protein function can be identified by the number of tms and the characteristics of loop lengths, i.e. BTPs.

Data Interpretation, Statistical↗

PubMed2004

C. elegans PAR proteins function by mobilizing and stabilizing asymmetrically localized protein complexes.

BACKGROUND: The PAR proteins are part of an ancient and widely conserved machinery for polarizing cells during animal development. Here we use a combination of genetics and live imaging methods in the model organism Caenorhabditis elegans to dissect the cellular mechanisms by which PAR proteins polarize cells. RESULTS: We demonstrate two distinct mechanisms by which PAR proteins polarize the C. elegans zygote. First, we show that several components of the PAR pathway function in intracellular motility, producing a polarized movement of the cell cortex. We present evidence that this cortical motility may drive the movement of cellular components that must become asymmetrically distributed, including both germline-specific ribonucleoprotein complexes and cortical domains containing the PAR proteins themselves. Second, PAR-1 functions to refine the asymmetric localization of germline ribonucleoprotein complexes by selectively stabilizing only those complexes that reach the PAR-1-enriched posterior cell cortex during the period of cortical motility. CONCLUSIONS: These results identify two cellular mechanisms by which the PAR proteins polarize the C. elegans zygote, and they suggest mechanisms by which PAR proteins may polarize cells in diverse animal systems.

14-3-3 Proteins↗

PubMed2005

Transthyretin-related proteins function to facilitate the hydrolysis of 5-hydroxyisourate, the end product of the uricase reaction.

Purine catabolic pathway in Bacillus subtilis is consisted of more than 14 genes. Among these genes, pucL and pucM are required for uricase activity. While PucL is known to encode the uricase itself, the function of PucM is still unclear although this protein is also indispensable for uric acid decomposition. Here, we provide evidence that PucM, a transthyretin-related protein, functions to facilitate the hydrolysis of 5-hydroxyisourate, the end product of the uricase reaction. Based on these results, we propose that transthyretin-related proteins present in diverse organisms are not functionally related to transthyretin but actually function as a hydroxyisourate hydrolase.

Amino Acid Sequence↗

PubMed2003

Flattening the glucocorticoid rhythm causes changes in hippocampal expression of messenger RNAs coding structural and functional proteins: implications for aging and depression.

Subtle changes in glucocorticoid levels, including a flattening of the diurnal rhythm with raised nadir, are prevalent, being characteristic of both aging and major depression. Both these conditions are also associated with deficits in hippocampally mediated cognitive functions. We hypothesized that this profile of glucocorticoid levels causes structural and functional changes in the hippocampus, which in turn may engender cognitive deficits. We implanted slow-release corticosterone pellets into adrenally intact adult male rats to produce a flattened glucocorticoid rhythm with levels clamped midway between the normal nadir and zenith. Using density profile analysis we measured hippocampal expression of messenger RNAs encoding structural and functional proteins. In rats with a flattened glucocorticoid rhythm, the expression of the mRNA coding for microtubule associated protein-2b (MAP2b) was reduced in CA3 relative to sham-operated controls, but unchanged in dentate gyrus and CA1. In contrast, the expression of the mRNA coding the alpha subunit of calcium-calmodulin dependent kinase (CAMKIIalpha) was reduced in dentate gyrus in animals with a flattened glucocorticoid rhythm, but unchanged in CA3. The expression of the mRNA coding the synaptic vesicle protein synaptophysin was unchanged in both CA3 and dentate gyrus. The data indicate that a flattening of the normal diurnal glucocorticoid rhythm decreases the hippocampal expression of mRNAs coding key structural and functional proteins, and does so in a regionally selective manner. The data may have relevance for cognitive deficits characteristic of aging and depression.

Aging↗

PubMed1998

Acute femoral artery thrombosis associated with functional protein C deficiency as the presenting manifestation of acute monocytic leukemia.

Acute leukemia may be linked to disturbances of the coagulation system, which are usually due to hyperviscosity because of disseminated intravascular coagulation or a high white cell count. We report a unique case of femoral artery thrombosis as the beginning symptom of acute monocytic leukemia (M5) associated with a low level of functional protein C. The patient had multiple recurrent episodes of thrombosis with low levels of functional protein C associated with the relapse of the leukemia. A review of the literature shows that this is an extremely rare phenomenon.

Acute Disease↗

PubMed2006

Revisiting the prediction of protein function at CASP6.

The ability to predict the function of a protein, given its sequence and/or 3D structure, is an essential requirement for exploiting the wealth of data made available by genomics and structural genomics projects and is therefore raising increasing interest in the computational biology community. To foster developments in the area as well as to establish the state of the art of present methods, a function prediction category was tentatively introduced in the 6th edition of the Critical Assessment of Techniques for Protein Structure Prediction (CASP) worldwide experiment. The assessment of the performance of the methods was made difficult by at least two factors: (a) the experimentally determined function of the targets was not available at the time of assessment; (b) the experiment is run blindly, preventing verification of whether the convergence of different predictions towards the same functional annotation was due to the similarity of the methods or to a genuine signal detectable by different methodologies. In this work, we collected information about the methods used by the various predictors and revisited the results of the experiment by verifying how often and in which cases a convergent prediction was obtained by methods based on different rationale. We propose a method for classifying the type and redundancy of the methods. We also analyzed the cases in which a function for the target protein has become available. Our results show that predictions derived from a consensus of different methods can reach an accuracy as high as 80%. It follows that some of the predictions submitted to CASP6, once reanalyzed taking into account the type of converging methods, can provide very useful information to researchers interested in the function of the target proteins.

Caspase 6↗

PubMed1992

Endotoxin tolerance is associated with altered GTP-binding protein function.

Previous studies have suggested that guanine nucleotide regulatory (G) proteins modulate endotoxin-stimulated peritoneal macrophage arachidonic acid (AA) metabolism. Endotoxin-stimulated metabolism of AA by peritoneal macrophages is decreased in endotoxin tolerance (Rogers et al. Prostaglandins 31: 639-650, 1986). These observations led to a study of G protein function and AA metabolism by peritoneal macrophages in endotoxin tolerance. Endotoxin tolerance was induced by the administration of sublethal doses of endotoxin. AA metabolism was assessed by measurement of thromboxane B2 (TxB2), a cyclooxygenase metabolite. NaF (5 mM), an activator of G proteins, significantly stimulated TxB2 synthesis in control macrophages from 7.7 +/- 0.2 to 19.1 +/- 0.6 (SE) ng/ml (P less than 0.05) at 2 h and was partially inhibited by pertussis toxin, suggesting a G protein-dependent mechanism. Salmonella enteritidis endotoxin (50 micrograms/ml) stimulated a similar increase in TxB2 levels (23 +/- 0.4 ng/ml, P less than 0.05). In contrast to control macrophages, macrophages from endotoxin-tolerant rats stimulated with either NaF or S. enteritidis endotoxin had TxB2 levels that were only 30 and 2% of the respective stimulated control cells. Basal guanosine-triphosphatase (GTPase) activity (33 +/- 6 pmol.mg-1.min-1) in endotoxin-tolerant macrophage membranes was significantly lower (P less than 0.05) than control basal activity (158 +/- 5 pmol.mg-1.min-1). This suppression of macrophage GTPase activity was apparent 48 h after the first in vivo sublethal endotoxin injection (100 micrograms/kg ip). The reduced GTPase activity paralleled in vitro cellular hyporesponsiveness to endotoxin-stimulated TxB2 production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

The C-terminal sequence of LMADS1 is essential for the formation of homodimers for B function proteins.

LMADS1, a lily (Lilium longiflorum) AP3 orthologue, contains the complete consensus sequence of the paleoAP3 (YGSHDLRLA) and PI-derived (YEFRVQPSQPNLH) motifs in the C-terminal region of the protein. Interestingly, through yeast two-hybrid analysis, LMADS1 was found to be capable of forming homodimers. These results indicated that LMADS1 represents an ancestral form of the B function protein, which retains the ability to form homodimers in regulating petal and stamen development in lily. To explore the involvement of the conserved motifs in the C-terminal region of LMADS1 in forming homodimers, truncated forms of LMADS1 were generated, and their ability to form homodimers was analyzed using yeast two-hybrid and electrophoretic mobility shift assay. The ability of LMADS1 to form homodimers decreased once the C-terminal paleoAP3 motif was deleted. When both paleoAP3 and PI-derived motifs were deleted, the ability of LMADS1 to form homodimers was completely abolished. This result indicated that although the paleoAP3 motif promotes the formation of LMADS1 homodimers, the PI-derived motif is essential. Deletion analysis indicated that two amino acids, RV, of the 5 final amino acids, YEFRV, in the PI-derived motif are essential for the formation of homodimers. Further, point mutation analysis indicated that amino acid Val was absolutely necessary, whereas residue Arg played a less important role in the formation of homodimers. Furthermore, Arabidopsis AP3 was able to form homodimers once its C-terminal region was replaced by that of LMADS1. This result indicated that the C-terminal region of LMADS1 is responsible and essential for homodimer formation of the ancestral form of the B function protein.

Amino Acid Motifs↗

PubMedDate not supplied

Protein-functionalized polymer brushes.

A new strategy for the preparation of protein-functionalized polymer brushes is reported, which is based on a combination of surface-initiated atom transfer radical polymerization (ATRP), p-nitrophenyl chloroformate activation of the surface hydroxyl groups, and subsequent O(6)-benzylguanine (BG) functionalization. The BG-functionalized brushes are used to chemoselectively immobilize O(6)-alkylguanine-DNA-alkyltransferase (AGT) fusion proteins with a defined orientation and surface density. These protein-modified polymer brushes are attractive candidates for the development of protein microarrays.

Polymers↗

PubMed1997

Two-dimensional arrangement of a functional protein by cysteine-gold interaction: enzyme activity and characterization of a protein monolayer on a gold substrate.

We have characterized the functional protein, myosin subfragment 1 (S1), attached to a gold substrate by the sulfhydryl groups of cysteine in proteins. The amino groups of the regulatory light chain (RLC) isolated from myosin were labeled with a radioisotope (125I), and the labeled RLC was incorporated into S1 from which the RLC had been removed. The radiation from 125I showed that S1 molecules had attached to the gold and, through the interference effect of the monochromatic radiation from 125I, provided information about the position of labeled RLC sites in the S1 monolayer. The interference fringes showed that the RLC was located close to the gold surface and that all of the adsorbed S1 molecules had the same orientation. We confirmed that the motor function of S1 on the gold surface is maintained by observing sliding movement at low ionic strength and by observing the detachment at high ionic strength of fluorescent actin filaments in the presence of ATP. We also found that the adsorbed S1 molecules were not removed from the Au surface by a reducing agent. Thus the Au-S bond is more stable than the S-S bond.

Actins↗

PubMed2006

Tobacco mosaic virus movement protein functions as a structural microtubule-associated protein.

The cell-to-cell spread of Tobacco mosaic virus infection depends on virus-encoded movement protein (MP), which is believed to form a ribonucleoprotein complex with viral RNA (vRNA) and to participate in the intercellular spread of infectious particles through plasmodesmata. Previous studies in our laboratory have provided evidence that the vRNA movement process is correlated with the ability of the MP to interact with microtubules, although the exact role of this interaction during infection is not known. Here, we have used a variety of in vivo and in vitro assays to determine that the MP functions as a genuine microtubule-associated protein that binds microtubules directly and modulates microtubule stability. We demonstrate that, unlike MP in whole-cell extract, microtubule-associated MP is not ubiquitinated, which strongly argues against the hypothesis that microtubules target the MP for degradation. In addition, we found that MP interferes with kinesin motor activity in vitro, suggesting that microtubule-associated MP may interfere with kinesin-driven transport processes during infection.

Cells, Cultured↗