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91.
Kristiansen S Richter EA 《American journal of physiology. Endocrinology and metabolism》2002,283(2):E374-E382
We have previously developed a cell-free assay from rat skeletal muscle that displayed in vitro glucose transporter 4 (GLUT4) transfer from large to small membrane structures by the addition of a cytosolic protein fraction. By combining protein fractionation and the in vitro GLUT4 transfer assay, we have purified a glycosylphosphatidylinositol (GPI) phospholipase D (PLD) that induces transfer of GLUT4 from small to large membranes. The in vitro GLUT4 transfer was activated and inhibited by suramin and 1,10-phenanthroline (an activator and an inhibitor of GPI-PLD activity, respectively). Furthermore, upon purification of the GLUT4 transporter protein, the protein displayed an elution profile in which the molecular mass was related to the charge, suggesting the presence or absence of phosphate. Second, by photoaffinity labeling of the purified GLUT4 with 3-(trifluoromethyl)-3-(m-[(125)I]iodopenyl)diazirine, both labeled phosphatidylethanolamine and fatty acids (constituents of a GPI link) were recovered. Third, by using phase transition of Triton X-114, the purified GLUT4 was found to be partly detergent resistant, which is a known characteristic of GPI-linked proteins. Fourth, the purified GLUT4 protein was recognized by an antibody raised specifically against GPI links. In conclusion, GLUT4-containing vesicles may be released from a membrane compartment by action of a GPI-PLD. 相似文献
92.
93.
Doa4 is a ubiquitin-specific protease in Saccharomyces cerevisiae that deubiquitinates integral membrane proteins sorted into the lumenal vesicles of late-endosomal multivesicular bodies (MVBs). We show that the non-catalytic N terminus of Doa4 mediates its recruitment to endosomes through its association with Bro1, which is one of several highly conserved class E Vps proteins that comprise the core MVB sorting machinery. In turn, Bro1 directly stimulates deubiquitination by interacting with a YPxL motif in the catalytic domain of Doa4. Mutations in either Doa4 or Bro1 that disrupt catalytic activation of Doa4 impair deubiquitination and sorting of MVB cargo proteins and lead to the formation of lumenal MVB vesicles that are predominantly small compared with the vesicles seen in wild-type cells. Thus, by recruiting Doa4 to late endosomes and stimulating its catalytic activity, Bro1 fulfills a novel dual role in coordinating deubiquitination in the MVB pathway. 相似文献
94.
95.
Summary On a soil rich in CaCO3 in a semiaride climate in Algeria a hard soil layer, impermeable for plant roots, was formed in a depth of 20–40 cm after
farmyard manure application and irrigation.
To find the reason soil samples of this field were taken and leaching experiments were carried out in the laboratory, with
the result that much more Caions and HCO3-ions were leached out of the soils with farmyard manure application than from the soils without manure.
Probably the high amount of CO2, being liberated by the organic matter, and the irrigation water dissolved the CaCO3 in the soil, and the formed Ca- and HCO3-ions followed the movement of water in the soil. Where the Ca(HCO3)2 reached soil layers with a less amount of CO2, CaCO3 precipitated and formed the hard soil layer.
In order to avoid the formation of such calcareous crusts on irrigated, limy soils in a dry climate it is recommended to fertilize
rather often small quantities instead of rarely big quantities of farmyard manure. 相似文献
96.
97.
The stromal processing peptidase (SPP) catalyzes removal of transit peptides from a diversity of precursor proteins imported into chloroplasts. SPP contains an HXXEH zinc-binding motif characteristic of members of the metallopeptidase family M16. We previously found that the three steps of precursor processing by SPP (i.e. transit peptide binding, removal, and conversion to a degradable subfragment) are mediated by features that reside in the C-terminal 10-15 residues of the transit peptide. In this study, we performed a mutational analysis of SPP to identify structural elements that determine its function. SPP loses the ability to proteolytically remove the transit peptide when residues of the HXXEH motif, found in an N-terminal region, are mutated. Deletion of 240 amino acids from its C terminus also abolishes activity. Interestingly, however, SPP can still carry out the initial binding step, recognizing the C-terminal residues of the transit peptide. Hence, transit peptide binding and removal are two separable steps of the overall processing reaction. Transit peptide conversion to a subfragment also depends on the HXXEH motif. The precursor of SPP, containing an unusually long transit peptide itself, is not proteolytically active. Thus, the SPP precursor is synthesized as a latent form of the metallopeptidase. 相似文献
98.
Fabian Richter Oliver Seifert Andreas Herrmann Klaus Pfizenmaier Roland E. Kontermann 《MABS-AUSTIN》2019,11(4):653-665
The development of alternative therapeutic strategies to tumor necrosis factor (TNF)-blocking antibodies for the treatment of inflammatory diseases has generated increasing interest. In particular, selective inhibition of TNF receptor 1 (TNFR1) promises a more precise intervention, tackling only the pro-inflammatory responses mediated by TNF while leaving regenerative and pro-survival signals transduced by TNFR2 untouched. We recently generated a monovalent anti-TNFR1 antibody fragment (Fab 13.7) as an efficient inhibitor of TNFR1. To improve the pharmacokinetic properties of Fab 13.7, the variable domains of the heavy and light chains were fused to the N-termini of newly generated heterodimerizing Fc chains. This novel Fc heterodimerization technology, designated “Fc-one/kappa” (Fc1κ) is based on interspersed constant Ig domains substituting the CH3 domains of a γ1 Fc. The interspersed immunoglobulin (Ig) domains originate from the per se heterodimerizing constant CH1 and CLκ domains and contain sequence stretches of an IgG1 CH3 domain, destined to enable interaction with the neonatal Fc receptor, and thus promote extended serum half-life. The resulting monovalent Fv-Fc1κ fusion protein (Atrosimab) retained strong binding to TNFR1 as determined by enzyme-linked immunosorbent assay and quartz crystal microbalance, and potently inhibited TNF-induced activation of TNFR1. Atrosimab lacks agonistic activity for TNFR1 on its own and in the presence of anti-human IgG antibodies and displays clearly improved pharmacokinetic properties. 相似文献
99.
Cryo-electron microscopy of vitreous sections 总被引:10,自引:0,他引:10
Al-Amoudi A Chang JJ Leforestier A McDowall A Salamin LM Norlén LP Richter K Blanc NS Studer D Dubochet J 《The EMBO journal》2004,23(18):3583-3588
Since the beginning of the 1980s, cryo-electron microscopy of a thin film of vitrified aqueous suspension has made it possible to observe biological particles in their native state, in the absence of the usual artefacts of dehydration and staining. Combined with 3-d reconstruction, it has become an important tool for structural molecular biology. Larger objects such as cells and tissues cannot generally be squeezed in a thin enough film. Cryo-electron microscopy of vitreous sections (CEMOVIS) provides then a solution. It requires vitrification of a sizable piece of biological material and cutting it into ultrathin sections, which are observed in the vitrified state. Each of these operations raises serious difficulties that have now been overcome. In general, the native state seen with CEMOVIS is very different from what has been seen before and it is seen in more detail. CEMOVIS will give its full potential when combined with computerized electron tomography for 3-d reconstruction. 相似文献
100.
Stephan Wilmes Oliver Beutel Zhi Li Véronique Francois-Newton Christian P. Richter Dennis Janning Cindy Kroll Patrizia Hanhart Katharina H?tte Changjiang You Gilles Uzé Sandra Pellegrini Jacob Piehler 《The Journal of cell biology》2015,209(4):579-593
Type I interferons (IFNs) activate differential cellular responses through a shared cell surface receptor composed of the two subunits, IFNAR1 and IFNAR2. We propose here a mechanistic model for how IFN receptor plasticity is regulated on the level of receptor dimerization. Quantitative single-molecule imaging of receptor assembly in the plasma membrane of living cells clearly identified IFN-induced dimerization of IFNAR1 and IFNAR2. The negative feedback regulator ubiquitin-specific protease 18 (USP18) potently interferes with the recruitment of IFNAR1 into the ternary complex, probably by impeding complex stabilization related to the associated Janus kinases. Thus, the responsiveness to IFNα2 is potently down-regulated after the first wave of gene induction, while IFNβ, due to its ∼100-fold higher binding affinity, is still able to efficiently recruit IFNAR1. Consistent with functional data, this novel regulatory mechanism at the level of receptor assembly explains how signaling by IFNβ is maintained over longer times compared with IFNα2 as a temporally encoded cause of functional receptor plasticity. 相似文献