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31.
Lucio Gomes Roman I Koning Dmitri I Svergun Abraham J Koster David C Fritzinger Carl‐Wilhelm Vogel Piet Gros 《The EMBO journal》2009,28(16):2469-2478
Immune protection by the complement system critically depends on assembly of C3 convertases on the surface of pathogens and altered host cells. These short‐lived protease complexes are formed through pro‐convertases, which for the alternative pathway consist of the complement component C3b and the pro‐enzyme factor B (FB). Here, we present the crystal structure at 2.2‐Å resolution, small‐angle X‐ray scattering and electron microscopy (EM) data of the pro‐convertase formed by human FB and cobra venom factor (CVF), a potent homologue of C3b that generates more stable convertases. FB is loaded onto CVF through its pro‐peptide Ba segment by specific contacts, which explain the specificity for the homologous C3b over the native C3 and inactive products iC3b and C3c. The protease segment Bb binds the carboxy terminus of CVF through the metal‐ion dependent adhesion site of the Von Willebrand factor A‐type domain. A possible dynamic equilibrium between a ‘loading’ and ‘activation’ state of the pro‐convertase may explain the observed difference between the crystal structure of CVFB and the EM structure of C3bB. These insights into formation of convertases provide a basis for further development of complement therapeutics. 相似文献
32.
Kock MA Hew BE Bammert H Fritzinger DC Vogel CW 《The Journal of biological chemistry》2004,279(29):30836-30843
Cobra venom factor (CVF) is the complement-activating protein from cobra venom. It is a structural and functional analog of complement component C3. CVF functionally resembles C3b, the activated form of C3. Like C3b, CVF binds factor B, which is subsequently cleaved by factor D to form the bimolecular complex CVF,Bb. CVF,Bb is a C3/C5 convertase that cleaves both complement components C3 and C5. CVF is a three-chain protein that structurally resembles the C3b degradation product C3c, which is unable to form a C3/C5 convertase. Both C3 and CVF are synthesized as single-chain prepro-proteins. This study reports the recombinant expression of pro-CVF in two insect cell expression systems (baculovirus-infected Sf9 Spodoptera frugiperda cells and stably transfected S2 Drosophila melanogaster cells). In both expression systems pro-CVF is synthesized initially as a single-chain pro-CVF molecule that is subsequently proteolytically processed into a two-chain form of pro-CVF that structurally resembles C3. The C3-like form of pro-CVF can be further proteolytically processed into another two-chain form of pro-CVF that structurally resembles C3b. Unexpectedly, all three forms of pro-CVF exhibit functional activity of mature, natural CVF. Recombinant pro-CVF supports the activation of factor B in the presence of factor D and Mg2+ and depletes serum complement activity like natural CVF. The bimolecular convertase pro-CVF,Bb exhibits both C3 cleaving and C5 cleaving activity. The activity of pro-CVF and the resulting C3/C5 convertase is indistinguishable from CVF and the CVF,Bb convertase. The ability to produce active forms of pro-CVF recombinantly ensures the continued availability of an important research reagent for complement depletion because cobra venom as the source for natural CVF will be increasingly difficult to obtain as the Indian cobra is on the list of endangered species. Experimental systems to express pro-CVF recombinantly will also be invaluable for studies to delineate the structure and function relationship of CVF and its differences from C3 as well as to generate human C3 derivatives with CVF-like function for therapeutic complement depletion ("humanized CVF"). 相似文献
33.
The nucleotide sequence of the tnpA gene completes the sequence of the Pseudomonas transposon Tn501. 总被引:7,自引:2,他引:5 下载免费PDF全文
The nucleotide sequence of the gene (tnpA) which codes for the transposase of transposon Tn501 has been determined. It contains an open reading frame for a polypeptide of Mr = 111,500, which terminates within the inverted repeat sequence of the transposon. The reading frame would be transcribed in the same direction as the mercury-resistance genes and the tnpR gene. The amino acid sequence predicted from this reading frame shows 32% identity with that of the transposase of the related transposon Tn3. The C-terminal regions of these two polypeptides show slightly greater homology than the N-terminal regions when conservative amino acid substitutions are considered. With this sequence determination, the nucleotide sequence of Tn501 is fully defined. The main features of the sequence are briefly presented. 相似文献
34.
Hidenori Takahashi Shigetaka Shimodaira Masahiro Ogasawara Shuichi Ota Masanori Kobayashi Hirofumi Abe Yuji Morita Kazuhiro Nagai Shunichi Tsujitani Masato Okamoto Yukio Suzuki Yoichi Nakanishi Yoshikazu Yonemitsu for the DC Vaccine Study Group at the Japanese Society of Immunotherapy Cell Therapy 《Cancer immunology, immunotherapy : CII》2016,65(9):1099-1111
35.
Walter RB; Rolig RL; Kozak KA; McEntire B; Morizot DC; Nairn RS 《Molecular biology and evolution》1993,10(6):1227-1238
Fishes represent the stem vertebrate condition and have maintained several
gene arrangements common to mammalian genomes throughout the 450 Myr of
divergence from a common ancestor. One such syntenic arrangement includes
the GPI-PEPD enzyme association on Xiphophorus linkage group IV and human
chromosome 19. Previously we assigned the Xiphophorus homologue of the
human ERCC2 gene to linkage group U5 in tight association with the CKM
locus. CKM is also tightly linked to the ERCC2 locus on human chromosome
19, leading to speculation that human chromosome 19 may have arisen by
fusion of two ancestral linkage groups which have been maintained in
fishes. To investigate this hypothesis further, we isolated and sequenced
Xiphophorus fish genomic regions exhibiting considerable sequence
similarity to the human DNA ligase 1 amino acid sequence. Comparison of the
fish DNA ligase sequence with those of other species suggests several modes
of amino acid conservation in this gene. A 2.2-kb restriction fragment
containing part of an X. maculatus DNA ligase 1 exon was used in backcross
hybrid mapping with 12 enzyme or RFLP loci. Significant linkage was
observed between the nucleoside phosphorylase (NP2) and the DNA ligase
(LIG1) loci on Xiphophorus linkage group VI. This assignment suggests that
the association of four DNA repair-related genes on human chromosome 19 may
be the result of chance chromosomal rearrangements.
相似文献
36.
Restriction mapping and sequencing have shown that humans have
substantially lower levels of mitochondrial genome diversity (d) than
chimpanzees. In contrast, humans have substantially higher levels of
heterozygosity (H) at protein-coding loci, suggesting a higher level of
diversity in the nuclear genome. To investigate the discrepancy further, we
sequenced a segment of the mitochondrial genome control region (CR) from 49
chimpanzees. The majority of these were from the Pan troglodytes versus
subspecies, which was underrepresented in previous studies. We also
estimated the average heterozygosity at 60 short tandem repeat (STR) loci
in both species. For a total sample of 115 chimpanzees, d = 0.075 +/0
0.037, compared to 0.020 +/- 0.011 for a sample of 1,554 humans. The
heterozygosity of human STR loci is significantly higher than that of
chimpanzees. Thus, the higher level of nuclear genome diversity relative to
mitochondrial genome diversity in humans is not restricted to
protein-coding loci. It seems that humans, not chimpanzees, have an unusual
d/H ratio, since the ratio in chimpanzees is similar to that in other
catarrhines. This discrepancy in the relative levels of nuclear and
mitochondrial genome diversity in the two species cannot be explained by
differences in mutation rate. However, it may result from a combination of
factors such as a difference in the extent of sex ratio disparity, the
greater effect of population subdivision on mitochondrial than on nuclear
genome diversity, a difference in the relative levels of male and female
migration among subpopulations, diversifying selection acting to increase
variation in the nuclear genome, and/or directional selection acting to
reduce variation in the mitochondrial genome.
相似文献
37.
38.
Roman Nepomuceno Matthew Zeglinski Jordyn Lerner Wlodzimierz Czarnecki Iain DC Kirkpatrick Jacek Strzelczyk Davinder S Jassal 《Cardiovascular ultrasound》2011,9(1):1-3
Partial anomalous pulmonary venous connection (PAPVC) is an extremely rare congenital condition where one or more of the pulmonary veins are connected to the venous circulation. Although initially suspected with unexplained right ventricular enlargement on transthoracic echocardiography (TTE), cardiac MRI is able to delineate the anatomical variant. We present a case of a 65-year-old male diagnosed with left sided PAPVC using multimodality cardiac imaging. 相似文献
39.
Flávia R Rocha Flávia S Papini-Terzi Milton Y Nishiyama Jr Ricardo ZN Vêncio Renato Vicentini Rodrigo DC Duarte Vicente E de Rosa Jr Fabiano Vinagre Carla Barsalobres Ane H Medeiros Fabiana A Rodrigues Eugênio C Ulian Sônia M Zingaretti João A Galbiatti Raul S Almeida Antonio VO Figueira Adriana S Hemerly Marcio C Silva-Filho Marcelo Menossi Gláucia M Souza 《BMC genomics》2007,8(1):1-22
40.
Eduardo DC Gonçalves Vânia Luiza D Bonato Denise M da Fonseca Edson G Soares Izaíra T Brandão Ana Paula M Soares Célio L Silva 《Genetic vaccines and therapy》2007,5(1):1-14
Vaccines are considered by many to be one of the most successful medical interventions against infectious diseases. But many significant obstacles remain, such as optimizing DNA vaccines for use in humans or large animals. The amount of doses, route and easiness of administration are also important points to consider in the design of new DNA vaccines. Heterologous prime-boost regimens probably represent the best hope for an improved DNA vaccine strategy. In this study, we have shown that heterologous prime-boost vaccination against tuberculosis (TB) using intranasal BCG priming/DNA-HSP65 boosting (BCGin/DNA) provided significantly greater protection than that afforded by a single subcutaneous or intranasal dose of BCG. In addition, BCGin/DNA immunization was also more efficient in controlling bacterial loads than were the other prime-boost schedules evaluated or three doses of DNA-HSP65 as a naked DNA. The single dose of DNA-HSP65 booster enhanced the immunogenicity of a single subcutaneous BCG vaccination, as evidenced by the significantly higher serum levels of anti-Hsp65 IgG2a Th1-induced antibodies, as well as by the significantly greater production of IFN-γ by antigen-specific spleen cells. The BCG prime/DNA-HSP65 booster was also associated with better preservation of lung parenchyma. The improvement of the protective effect of BCG vaccine mediated by a DNA-HSP65 booster suggests that our strategy may hold promise as a safe and effective vaccine against TB. 相似文献