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Efficient Recognition (efficient + recognition)
Selected AbstractsEfficient recognition of protein fold at low sequence identity by conservative application of Psi-BLAST: validation,JOURNAL OF MOLECULAR RECOGNITION, Issue 2 2005F. J. Stevens Abstract A substantial fraction of protein sequences derived from genomic analyses is currently classified as representing ,hypothetical proteins of unknown function'. In part, this reflects the limitations of methods for comparison of sequences with very low identity. We evaluated the effectiveness of a Psi-BLAST search strategy to identify proteins of similar fold at low sequence identity. Psi-BLAST searches for structurally characterized low-sequence-identity matches were carried out on a set of over 300 proteins of known structure. Searches were conducted in NCBI's non-redundant database and were limited to three rounds. Some 614 potential homologs with 25% or lower sequence identity to 166 members of the search set were obtained. Disregarding the expect value, level of sequence identity and span of alignment, correspondence of fold between the target and potential homolog was found in more than 95% of the Psi-BLAST matches. Restrictions on expect value or span of alignment improved the false positive rate at the expense of eliminating many true homologs. Approximately three-quarters of the putative homologs obtained by three rounds of Psi-BLAST revealed no significant sequence similarity to the target protein upon direct sequence comparison by BLAST, and therefore could not be found by a conventional search. Although three rounds of Psi-BLAST identified many more homologs than a standard BLAST search, most homologs were undetected. It appears that more than 80% of all homologs to a target protein may be characterized by a lack of significant sequence similarity. We suggest that conservative use of Psi-BLAST has the potential to propose experimentally testable functions for the majority of proteins currently annotated as ,hypothetical proteins of unknown function';. Copyright © 2004 John Wiley & Sons, Ltd. [source] Efficient recognition of protein fold at low sequence identity by conservative application of Psi-BLAST: application,JOURNAL OF MOLECULAR RECOGNITION, Issue 2 2005F. J. Stevens Abstract Based on a study involving structural comparisons of proteins sharing 25% or less sequence identity, three rounds of Psi-BLAST appear capable of identifying remote evolutionary homologs with greater than 95% confidence provided that more than 50% of the query sequence can be aligned with the target sequence. Since it seems that more than 80% of all homologous protein pairs may be characterized by a lack of significant sequence similarity, the experimental biologist is often confronted with a lack of guidance from conventional homology searches involving pair-wise sequence comparisons. The ability to disregard levels of sequence identity and expect value in Psi-BLAST if at least 50% of the query sequence has been aligned allows for generation of new hypotheses by consideration of matches that are conventionally disregarded. In one example, we suggest a possible evolutionary linkage between the cupredoxin and immunoglobulin fold families. A thermostable hypothetical protein of unknown function may be a circularly permuted homolog to phosphotriesterase, an enzyme capable of detoxifying organophosphate nerve agents. In a third example, the amino acid sequence of another hypothetical protein of unknown function reveals the ATP binding-site, metal binding site, and catalytic sidechain consistent with kinase activity of unknown specificity. This approach significantly expands the utility of existing sequence data to define the primary structure degeneracy of binding sites for substrates, cofactors and other proteins. Copyright © 2004 John Wiley & Sons, Ltd. [source] Selection for individual recognition and the evolution of polymorphic identity signals in Polistes paper waspsJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 3 2010M. J. SHEEHAN Abstract Individual recognition (IR) requires individuals to uniquely identify their social partners based on phenotypic variation. Because IR is so specific, distinctive phenotypes that stand out from the crowd facilitate efficient recognition. Over time, the benefits of unique appearances are predicted to produce a correlation between IR and phenotypic variation. Here, we test whether there is an association between elevated phenotypic polymorphism and IR in paper wasps. Previous work has shown that Polistes fuscatus use variable colour patterns for IR. We test whether two less variable wasp species, Polistes dominulus and Polistes metricus, are capable of IR. As predicted, neither species is capable of IR, suggesting that highly variable colour patterns are confined to Polistes species with IR. This association suggests that elevated phenotypic variation in taxa with IR may be the result of selection for identity signals rather than neutral processes. Given that IR is widespread among social taxa, selection for identity signalling may be an underappreciated mechanism for the origin and maintenance of polymorphism. [source] Structure of a new crystal form of tetraubiquitinACTA CRYSTALLOGRAPHICA SECTION D, Issue 2 2001Cynthia L. Phillips Polyubiquitin chains, in which the C-terminus and a lysine side chain of successive ubiquitin molecules are linked by an isopeptide bond, function to target substrate proteins for degradation by the 26S proteasome. Chains of at least four ubiquitin moieties appear to be required for efficient recognition by the 26S proteasome, although the conformations of the polyubiquitin chains recognized by the proteasome or by other enzymes involved in ubiquitin metabolism are currently unknown. A new crystal form of tetraubiquitin, which has two possible chain connectivities that are indistinguishable in the crystal, is reported. In one possible connectivity, the tetraubiquitin chain is extended and packs closely against the antiparallel neighbor chain in the crystal to conceal a hydrophobic surface implicated in 26S proteasome recognition. In the second possibility, the tetraubiqutitin forms a closed compact structure, in which that same hydrophobic surface is buried. Both of these conformations are quite unlike the structure of tetraubiquitin that was previously determined in a different crystal form [Cook et al. (1994), J. Mol. Biol.236, 601,609]. The new structure suggests that polyubiquitin chains may possess a substantially greater degree of conformational flexibility than has previously been appreciated. [source] A toll-like receptor 4 variant is associated with fatal outcome in children with invasive meningococcal diseaseACTA PAEDIATRICA, Issue 3 2009Joerg Faber Abstract Aims: Toll-like receptor 4 (TLR4) is the major endotoxin signalling receptor of the innate immune system and is required for efficient recognition of bacterial infections. Here, we analysed a possible association between the TLR4 variant Asp299Gly and disease outcome in children with invasive meningococcal disease. Methods: In total, 197 children with invasive meningococcal disease were analysed for the TLR4 Asp299Gly variant. Genotyping results were correlated with mortality, the frequency of ventilation support, application of inotropic substances, skin grafting, and limb loss. Results: The overall Asp299Gly allele frequency was 9.4%. Detection of a heterozygous Asp299Gly TLR4 mutation was significantly associated with fatal outcome (non-survivor group: 31.6% vs. survivor group: 12.1%; p = 0.021) and was even more pronounced in patients with disease onset less than 24 months of age (non-survivor group: 42.8% vs. survivor group: 10.2%; p = 0.006). In this age group, ventilation support was also more frequent in patients with the Asp299Gly genotype (37.5% vs. 6.2%). Conclusion: Our data suggest that the heterozygous TLR4 Asp299Gly genotype is associated with an increased mortality in children with invasive meningococcal disease. [source] | ||||||||||