排序方式: 共有25条查询结果,搜索用时 140 毫秒
21.
Tobias Wauer Kirby N Swatek Jane L Wagstaff Christina Gladkova Jonathan N Pruneda Martin A Michel Malte Gersch Christopher M Johnson Stefan MV Freund David Komander 《The EMBO journal》2015,34(3):307-325
The protein kinase PINK1 was recently shown to phosphorylate ubiquitin (Ub) on Ser65, and phosphoUb activates the E3 ligase Parkin allosterically. Here, we show that PINK1 can phosphorylate every Ub in Ub chains. Moreover, Ser65 phosphorylation alters Ub structure, generating two conformations in solution. A crystal structure of the major conformation resembles Ub but has altered surface properties. NMR reveals a second phosphoUb conformation in which β5-strand slippage retracts the C-terminal tail by two residues into the Ub core. We further show that phosphoUb has no effect on E1-mediated E2 charging but can affect discharging of E2 enzymes to form polyUb chains. Notably, UBE2R1- (CDC34), UBE2N/UBE2V1- (UBC13/UEV1A), TRAF6- and HOIP-mediated chain assembly is inhibited by phosphoUb. While Lys63-linked poly-phosphoUb is recognized by the TAB2 NZF Ub binding domain (UBD), 10 out of 12 deubiquitinases (DUBs), including USP8, USP15 and USP30, are impaired in hydrolyzing phosphoUb chains. Hence, Ub phosphorylation has repercussions for ubiquitination and deubiquitination cascades beyond Parkin activation and may provide an independent layer of regulation in the Ub system. 相似文献
22.
Optimization of mycophenolic acid production in solid state fermentation using response surface methodology 总被引:7,自引:0,他引:7
A K Sadhukhan MV Ramana Murthy R Ajaya Kumar E V S Mohan G Vandana C Bhar K Venkateswara Rao 《Journal of industrial microbiology & biotechnology》1999,22(1):33-38
Mycophenolic acid (MPA) can be produced in solid state fermentation. An isolate of Penicillium brevi-compactum ATCC 16024 grown on moist wheat bran produced a titre of 425 mg per kg of wheat bran. Central composite rotatable design
and response surface methodology were employed to derive a statistical model for media optimization towards production of
mycophenolic acid. Five levels with a five factorial design were adopted. The correlation coefficient was 0.82, ensuring a
satisfactory adjustment of the model to the experimental values. This statistical design was very effective in improving the
titre of mycophenolic acid up to 3286 mg per kg of wheat bran.
Received 24 July 1998/ Accepted in revised form 4 December 1998 相似文献
23.
Singh RA Zang YC Shrivastava A Hong J Wang GT Li S Tejada-Simon MV Kozovska M Rivera VM Zhang JZ 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(12):6393-6402
Th0 clones recognizing an immunodominant peptide of myelin basic protein (residues 83-99) were derived from patients with multiple sclerosis. We demonstrate that analogue peptides with alanine substitution at Val86 and His88 had a unique partial agonistic property in inducing Th0 -->Th1 and Th0 -->Th2 deviation of the myelin basic protein-reactive T cell clones, respectively. Th0 to Th1 deviation induced by peptide 86V-->A correlated with up-regulation of Fyn and ZAP-70 kinase activities. Conversely, Th0 to Th2 deviation induced by peptide 88H-->A was associated with complete failure to activate Fyn and ZAP-70 kinases. The observed Th1 and Th2 shift also correlated, to a lesser extent, with Lck kinase activity that was down-regulated with Th1 deviation and increased with Th2 deviation in some T cell clones. We demonstrated that the Th1 and Th2 shift induced by the analogue peptides was a reversible process, as the T cell clones previously exposed to either 86V-->A or 88H-->A peptide could revert to an opposite phenotype when rechallenged reciprocally with a different analogue peptide. The study has important implications in our understanding of regulation of TCR-associated tyrosine kinases by altered peptide ligands and its role in cytokine regulation of autoreactive T cells. 相似文献
24.
Reactivity and regulatory properties of human anti-idiotypic antibodies induced by T cell vaccination 总被引:8,自引:0,他引:8
Hong J Zang YC Tejada-Simon MV Li S Rivera VM Killian J Zhang JZ 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(12):6858-6864
Immunization with irradiated autoreactive T cells (T cell vaccination) induces anti-idiotypic T cell responses that preferentially recognize complementarity-determining region 3 sequences, contributing to clonal depletion of autoreactive T cells. However, it remains unknown whether T cell vaccination elicits anti-idiotypic humoral responses and whether the anti-idiotypic Abs play a similar role in the regulatory mechanism induced by T cell vaccination. In this study we examined the occurrence, the reactivity pattern, and the regulatory role of anti-idiotypic Abs elicited by T cell vaccination in patients with multiple sclerosis. We demonstrated for the first time that B cells producing anti-idiotypic Abs could be isolated from vaccinated patients. These EBV-transformed B cell lines were selected for specific reactivity to a 20-mer TCR peptide incorporating a common complementarity-determining region 3 sequence of the immunizing T cell clones. The resulting anti-idiotypic Abs were found to react with the original immunizing T cell clones and exhibit an inhibitory effect on their proliferation. The findings suggest that anti-idiotypic Ab responses can be induced by T cell vaccination in humans and that their regulatory properties are likely to contribute to the suppression of myelin basic protein-reactive T cells in vaccinated patients. The study has important implications in our understanding of the regulatory role of the anti-idiotypic humoral responses induced by T cell vaccination. 相似文献
25.
Sheila C Rahal Reinaldo S Volpi Carlos R Teixeira Vania MV Machado Guilherme DP Soares Carlos Ramires Neto Kathleen Linn 《BMC veterinary research》2012,8(1):1-5