Anomalous expansion of a polyglutamine (polyQ) tract in the protein ataxin-3 causes spinocerebellar ataxia type 3, an autosomal dominant neurodegenerative disease. Very little is known about the structure and the function of ataxin-3, although this information would undoubtedly help to understand why the expanded protein forms insoluble nuclear aggregates and causes neuronal cell death. With the aim of establishing the domain architecture of ataxin-3 and the role of the polyQ tract within the protein context, we have studied the human and murine orthologues using a combination of techniques, which range from limited proteolysis to circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopies. The two protein sequences share a highly conserved N-terminus and di¡er only in the length of the glutamine repeats and in the C-terminus. Our data conclusively indicate that ataxin-3 is composed by a structured N-terminal domain, followed by a £exible tail. Moreover, [15 N]glutamine selectively labelled samples allowed us to have a direct insight by NMR into the structure of the polyQ region. ß
An alternative route to plasmon-controlled fluorescence for improving the detection of fluorescence is proposed. In place of a metallic layer, a suitable silicon-based one-dimensional photonic crystal is used to generate a Bloch surface waves-coupled emission from a thin polymeric layer decorated with a fluorescent dye. Fluorescent radiation coupled to Bloch surface waves is strongly polarized and directional, with an angular divergence of 0.3° corresponding to a spectral bandwidth of 3 nm. Within this range, an overall signal enhancement of a factor larger than 500 is obtained as compared to a conventional glass substrate thanks to an additional enhancement mechanism based on dyes excitation via Bloch surface waves.
The PQBP1 (polyglutamine tract-binding protein 1) gene encodes a nuclear protein that regulates pre-mRNA splicing and transcription. Mutations in the PQBP1 gene were reported in several X chromosome-linked mental retardation disorders including Golabi-Ito-Hall syndrome. The missense mutation that causes this syndrome is unique among other PQBP1 mutations reported to date because it maps within a functional domain of PQBP1, known as the WW domain. The mutation substitutes tyrosine 65 with cysteine and is located within the conserved core of aromatic amino acids of the domain. We show here that the binding property of the Y65C-mutated WW domain and the full-length mutant protein toward its cognate proline-rich ligands was diminished. Furthermore, in GolabiIto-Hall-derived lymphoblasts we showed that the complex between PQBP1-Y65C and WBP11 (WW domain-binding protein 11) splicing factor was compromised. In these cells a substantial decrease in pre-mRNA splicing efficiency was detected. Our study points to the critical role of the WW domain in the function of the PQBP1 protein and provides an insight into the molecular mechanism that underlies the X chromosome-linked mental retardation entities classified globally as Renpenning syndrome.
Background: NHBA, a surface-exposed lipoprotein from Neisseria meningitidis, is part of a multicomponent vaccine against serogroup B meningitis.Results: We have solved the structure of a conserved C-terminal domain that adopts a β-barrel fold and seems to be the only independently folded region of the protein.Conclusion: We observed a significant structural similarity with other Nesseria proteins.Significance: Our data represent the first step toward understanding the structure/immunology relationship of NHBA.
a b s t r a c tWe present the innovative application of a Bloch surface wave based sensor to the detection of protein aggregation. In Hen Egg White Lysozyme (HEWL) solutions, aggregates are discriminated from the monomeric forms in a label-free detection scheme.
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