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111.
Bae JH Rubini M Jung G Wiegand G Seifert MH Azim MK Kim JS Zumbusch A Holak TA Moroder L Huber R Budisa N 《Journal of molecular biology》2003,328(5):1071-1081
Much effort has been dedicated to the design of significantly red shifted variants of the green fluorescent protein (GFP) from Aequoria victora (av). These approaches have been based on classical engineering with the 20 canonical amino acids. We report here an expansion of these efforts by incorporation of an amino substituted variant of tryptophan into the "cyan" GFP mutant, which turned it into a "gold" variant. This variant possesses a red shift in emission unprecedented for any avFP, similar to "red" FPs, but with enhanced stability and a very low aggregation tendency. An increasing number of non-natural amino acids are available for chromophore redesign (by engineering of the genetic code) and enable new general strategies to generate novel classes of tailor-made GFP proteins. 相似文献
112.
Translation of the minor capsid protein of a calicivirus is initiated by a novel termination-dependent reinitiation mechanism 总被引:8,自引:0,他引:8
Meyers G 《The Journal of biological chemistry》2003,278(36):34051-34060
Caliciviruses represent a family of positive strand RNA viruses responsible for a variety of syndromes in man and animals. VP10, a minor structural protein of the calicivirus rabbit hemorrhagic disease virus, is encoded in the small 3'-terminal open reading frame (ORF) 2 and is translated with an efficiency of approximately 20% of the preceding ORF1. The presence of the ORF1 termination codon is crucial for VP10 expression. Translation of VP10 starts at an AUG codon located at positions -5 to -3 of the ORF1 termination codon. However, VP10 was also expressed in the absence of an AUG initiation codon. The majority of ORF1 could be deleted or replaced by different sequences without significant influence on VP10 expression as long as translation terminated at the given position. The RNA sequence of the 3'-terminal 84 nucleotides of ORF1 but not the encoded peptide was found to be crucial for VP10 expression. In contrast, nearly the entire ORF2 could be replaced by a foreign sequence without abrogation of its translation. Accordingly, VP10 is expressed in a translation termination/reinitiation process that is particular because it is independent of an AUG translational start codon and requires the presence of a sequence element upstream of the initiation site. 相似文献
113.
Malovrh P Viero G Serra MD Podlesek Z Lakey JH Macek P Menestrina G Anderluh G 《The Journal of biological chemistry》2003,278(25):22678-22685
Equinatoxin II is a representative of actinoporins, eukaryotic pore-forming toxins from sea anemones. It creates pores in natural and artificial lipid membranes by an association of three or four monomers. Cysteine-scanning mutagenesis was used to study the structure of the N terminus, which is proposed to be crucial in transmembrane pore formation. We provide data for two steps of pore formation: a lipid-bound monomeric intermediate state and a final oligomeric pore. Results show that residues 10-28 are organized as an alpha-helix in both steps. In the first step, the whole region is transferred to a lipid-water interface, laying flat on the membrane. In the pore-forming state, the hydrophilic side of the amphipathic helix lines the pore lumen. The pore has a restriction around Asp-10, according to the permeabilization ratio of ions flowing through pores formed by chemically modified mutants. A general model was introduced to derive the tilt angle of the helix from the ion current data. This study reveals that actinoporins use a unique single helix insertion mechanism for pore formation. 相似文献
114.
HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course 总被引:7,自引:0,他引:7
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Barcellos LF Oksenberg JR Begovich AB Martin ER Schmidt S Vittinghoff E Goodin DS Pelletier D Lincoln RR Bucher P Swerdlin A Pericak-Vance MA Haines JL Hauser SL;Multiple Sclerosis Genetics Group 《American journal of human genetics》2003,72(3):710-716
Models of disease susceptibility in multiple sclerosis (MS) often assume a dominant action for the HLA-DRB1*1501 allele and its associated haplotype (DRB1*1501-DQB1*0602 or DR2). A robust and phenotypically well-characterized MS data set was used to explore this model in more detail. A dose effect of HLA-DR2 haplotypes on MS susceptibility was revealed. This observation suggests that, in addition to the role of HLA-DR2 in MS, two copies of a susceptibility haplotype further increase disease risk. Second, we report that DR2 haplotypes modify disease expression. There is a paucity of benign MS and an increase of severe MS in individuals homozygous for DR2. Concepts of the molecular mechanisms that underlie linkage and association of the human leukocyte antigen (HLA) region to MS need to be revised to accommodate these data. 相似文献
115.
The caspase-activated DNase (CAD) is an important nuclease involved in apoptotic DNA degradation. Results of a sequence comparison of CAD proteins with beta beta alpha-Me-finger nucleases in conjunction with a mutational and chemical modification analysis suggest that CAD proteins constitute a new family of beta beta alpha-Me-finger nucleases. Nucleases of this family have widely different functions but are characterized by a common active-site fold and similar catalytic mechanisms. According to our results and comparisons with related nucleases, the active site of CAD displays features that partly resemble those of the colicin E9 and partly those of the T4 endonuclease VII active sites. We suggest that the catalytic mechanism of CAD involves a conserved histidine residue, acting as a general base, and another histidine as well as an aspartic acid residue required for cofactor binding. Our findings provide a first insight into the likely active-site structure and catalytic mechanism of a nuclease involved in the degradation of chromosomal DNA during programmed cell death. 相似文献
116.
Effects of the eukaryotic pore-forming cytolysin Equinatoxin II on lipid membranes and the role of sphingomyelin
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Equinatoxin II (EqtII), a protein toxin from the sea anemone Actinia equina, readily creates pores in sphingomyelin-containing lipid membranes. The perturbation by EqtII of model lipid membranes composed of dimyristoylphosphatidycholine and sphingomyelin (10 mol %) was investigated using wideline phosphorus-31 and deuterium NMR. The preferential interaction between EqtII (0.1 and 0.4 mol %) and the individual bilayer lipids was studied by (31)P magic angle spinning NMR, and toxin-induced changes in bilayer morphology were examined by freeze-fracture electron microscopy. Both NMR and EM showed the formation of an additional lipid phase in sphingomyelin-containing mixed lipid multilamellar suspensions with 0.4 mol % EqtII. The new toxin-induced phase consisted of small unilamellar vesicles 20-40 nm in diameter. Deuterium NMR showed that the new lipid phase contains both dimyristoylphosphatidycholine and sphingomyelin. Solid-state (31)P NMR showed an increase in spin-lattice and a decrease in spin-spin relaxation times in mixed-lipid model membranes in the presence of EqtII, consistent with an increase in the intensity of low frequency motions. The (2)H and (31)P spectral intensity distributions confirmed a change in lipid mobility and showed the creation of an isotropic lipid phase, which was identified as the small vesicle structures visible by electron microscopy in the EqtII-lipid suspensions. The toxin appears to enhance slow motions in the membrane lipids and destabilize the membrane. This effect was greatly enhanced in sphingomyelin-containing mixed lipid membranes compared with pure phosphatidylcholine bilayers, suggesting a preferential interaction between the toxin and bilayer sphingomyelin. 相似文献
117.
Insulin receptor substrate p53/p58 (IRSp53) is involved in cytoskeletal dynamics and is a candidate disease sensor in polyglutamine expansion neurodegeneration. It is widely expressed throughout the body, but its levels are dramatically elevated in forebrain regions. IRSp53 functions as a signal transducing adaptor between activated Rho family GTPases and their effectors. There are four known alternatively spliced isoforms of IRSp53 that vary by the identity of the 3'-terminal exon. We report here that there is a fifth alternatively spliced isoform, IRSp53-B, which lacks 40 amino acids abutting the CRIB/SH3 (Cdc42/Rac-interactive binding/Src homology 3)-binding site. We speculate that the novel form has an altered function related to the mechanism of autoinactivation. IRSp53-B has an odd history in the mammalian lineage, which may complicate the use of rodent models to study cytoskeletal reorganization. 相似文献
118.
119.
Sigrist CJ Cerutti L Hulo N Gattiker A Falquet L Pagni M Bairoch A Bucher P 《Briefings in bioinformatics》2002,3(3):265-274
Among the various databases dedicated to the identification of protein families and domains, PROSITE is the first one created and has continuously evolved since. PROSITE currently consists of a large collection of biologically meaningful motifs that are described as patterns or profiles, and linked to documentation briefly describing the protein family or domain they are designed to detect. The close relationship of PROSITE with the SWISS-PROT protein database allows the evaluation of the sensitivity and specificity of the PROSITE motifs and their periodic reviewing. In return, PROSITE is used to help annotate SWISS-PROT entries. The main characteristics and the techniques of family and domain identification used by PROSITE are reviewed in this paper. 相似文献
120.
Mulder NJ Apweiler R Attwood TK Bairoch A Bateman A Binns D Biswas M Bradley P Bork P Bucher P Copley R Courcelle E Durbin R Falquet L Fleischmann W Gouzy J Griffith-Jones S Haft D Hermjakob H Hulo N Kahn D Kanapin A Krestyaninova M Lopez R Letunic I Orchard S Pagni M Peyruc D Ponting CP Servant F Sigrist CJ;InterPro Consortium 《Briefings in bioinformatics》2002,3(3):225-235