Three dimensional structure directs T-cell epitope dominance associated with allergy

Background

CD4+ T-cell epitope immunodominance is not adequately explained by peptide selectivity in class II major histocompatibility proteins, but it has been correlated with adjacent segments of conformational flexibility in several antigens.

Methods

The published T-cell responses to two venom allergens and two aeroallergens were used to construct profiles of epitope dominance, which were correlated with the distribution of conformational flexibility, as measured by crystallographic B factors, solvent-accessible surface, COREX residue stability, and sequence entropy.

Results

Epitopes associated with allergy tended to be excluded from and lie adjacent to flexible segments of the allergen.

Conclusion

During the initiation of allergy, the N- and/or C-terminal ends of proteolytic processing intermediates were preferentially loaded into antigen presenting proteins for the priming of CD4+ T cells.     

Colour-sidedness in Gloucester cattle is associated with a complex structural variant impacting regulatory elements downstream of KIT

Colour-sidedness is a striking coat colour pattern found in a number of cattle breeds, typically characterised by a white stripe that extends along the back, head and belly of the animal. This dominant phenotype is caused by two related translocations (Cs₆ and Cs₂₉) that alter a region downstream of the KIT gene. Gloucester cattle are native to the UK and are known for an unusual colour-sided pattern that does not extend to the head. We carried out whole-genome sequencing of two Gloucester bulls as well as colour-sided Irish Moiled, British White and Pustertaler Sprinzen for comparison. We found that the Gloucester cattle also have a complex structural variant downstream of KIT, which overlaps the regions involved in Cs₆ and Cs_29. All three alleles potentially disrupt a number of putative regulatory elements downstream of KIT. These results complement and expand on the recently published work focused on the Pinzgauer breed from Austria, a carrier of the same colour-sided pattern as seen in Gloucester cattle.     

Highly Sensitive SPR Sensor Based on Ag-ITO-BlueP/TMDCs-Graphene Heterostructure

Plasmonics - The novel surface plasmon resonance (SPR) sensor based on hybrid structure of Ag-indium tin oxide (ITO)-blue phosphorene (BlueP)/transition metal dichalcogenides (TMDCs)-graphene is...     

Within-population craniometric variability of insular populations of deer mice, Peromyscus maniculatus, elucidated by landscape configuration

Within-population genetic variability of twelve insular and four mainland populations of deer mice ( Peromyscus maniculatus ) was assessed using craniometric characters, and compared to results previously obtained from RAPD data. An index of Craniometric Variance ( CVar ) was computed from pairwise distances among all specimens. Variations in CVar measures were then compared to landscape variables using a linear regression approach. Our results suggest that CVar decreases in presence of large number of a competitive species (the boreal redback vole, Clethrionomys gapperi ; r =−0.527, p <0.037) in deer mouse populations. Island remoteness ( r =−0.251, p <0.220) and the geometry of the bank opposite to each island ( r =−0.459, p <0.067) were marginally correlated with CVar , but the linear combination of these two variables, forming a composite isolation index, represented the major factor explaining the observed CVar ( r =−0.648, p <0.011). Using a multiple regression model, 76.3% of the CVar was explained by a combination of this isolation index and the competitors' abundance. These results suggest that taking into account landscape barriers as well as the dispersal behavior of small mammals might provide sounder ecological variables than geographical distances alone for predicting within-population genetic variability in a network of habitat patches.     

Reduction of ferric green rust by Shewanella putrefaciens

AIMS: To reduce carbonated ferric green rust (GR*) using an iron respiring bacterium and obtain its reduced homologue, the mixed Fe(II)-Fe(III) carbonated green rust (GR). METHODS AND RESULTS: The GR* was chemically synthesized by oxidation of the GR and was incubated with Shewanella putrefaciens cells at a defined [Fe(III)]/[cell] ratio. Sodium methanoate served as the sole electron donor. The GR* was quickly transformed in GR (iron reducing rate = 8.7 mmol l(-1) h(-1)). CONCLUSIONS: Ferric green rust is available for S. putrefaciens respiration as an electron acceptor. The reversibility of the GR redox state can be driven by bacterial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This work suggests that GRs would act as an electronic balance in presence of bacteria. It provides also new perspectives for using iron reducing bacterial activity to regenerate the reactive form of GR during soil or water decontamination processes.     

Analysis of the DNA-binding sequence specificity of the archaeal transcriptional regulator Ss-LrpB from Sulfolobus solfataricus by systematic mutagenesis and high resolution contact probing

To determine the sequence specificity of dimeric Ss-LrpB, a high resolution contact map was constructed and a saturation mutagenesis conducted on one half of the palindromic consensus box. Premodification binding interference indicates that Ss-LrpB establishes most of its tightest contacts with a single strand of two major groove segments and interacts with the minor groove at the center of the box. The requirement for bending is reflected in the preference for an A+T rich center and confirmed with C.G and C.I substitutions. The saturation mutagenesis indicates that major groove contacts with C.G at position 5 and its symmetrical counterpart are most critical for the specificity and strength of the interaction. Conservation at the remaining positions improved the binding. Hydrogen bonding to the O6 and N7 acceptor atoms of the G5' residue play a major role in complex formation. Unlike many other DNA-binding proteins Ss-LrpB does not establish hydrophobic interactions with the methyls of thymine residues. The binding energies determined from the saturation mutagenesis were used to construct a sequence logo, which pin-points the overwhelming importance of C.G at position 5. The knowledge of the DNA-binding specificity will constitute a precious tool for the search of new physiologically relevant binding sites for Ss-LrpB in the genome.     

Crystal structure of the Actinomadura R39 DD-peptidase reveals new domains in penicillin-binding proteins

Actinomadura sp. R39 produces an exocellular DD-peptidase/penicillin-binding protein (PBP) whose primary structure is similar to that of Escherichia coli PBP4. It is characterized by a high beta-lactam-binding activity (second order rate constant for the acylation of the active site serine by benzylpenicillin: k2/K = 300 mm(-1) s(-1)). The crystal structure of the DD-peptidase from Actinomadura R39 was solved at a resolution of 1.8 angstroms by single anomalous dispersion at the cobalt resonance wavelength. The structure is composed of three domains: a penicillin-binding domain similar to the penicillin-binding domain of E. coli PBP5 and two domains of unknown function. In most multimodular PBPs, additional domains are generally located at the C or N termini of the penicillin-binding domain. In R39, the other two domains are inserted in the penicillin-binding domain, between the SXXK and SXN motifs, in a manner similar to "Matryoshka dolls." One of these domains is composed of a five-stranded beta-sheet with two helices on one side, and the other domain is a double three-stranded beta-sheet inserted in the previous domain. Additionally, the 2.4-angstroms structure of the acyl-enzyme complex of R39 with nitrocefin reveals the absence of active site conformational change upon binding the beta-lactams.     

Compensatory cis-trans evolution and the dysregulation of gene expression in interspecific hybrids of Drosophila

Hybrids between species are often characterized by novel gene-expression patterns. A recent study on allele-specific gene expression in hybrids between species of Drosophila revealed cases in which cis- and trans-regulatory elements within species had coevolved in such a way that changes in cis-regulatory elements are compensated by changes in trans-regulatory elements. We hypothesized that such coevolution should often lead to gene misexpression in the hybrid. To test this hypothesis, we estimated allele-specific expression and overall expression levels for 31 genes in D. melanogaster, D. simulans, and their F1 hybrid. We found that 13 genes with cis-trans compensatory evolution are in fact misexpressed in the hybrid. These represent candidate genes whose dysregulation might be the consequence of coevolution of cis- and trans-regulatory elements within species. Using a mathematical model for the regulation of gene expression, we explored the conditions under which cis-trans compensatory evolution can lead to misexpression in interspecific hybrids.