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51.
Letter: Preliminary x-ray data from well-ordered crystals of a human immunoglobulin G molecule 总被引:1,自引:0,他引:1
Crystals of an intact immunoglobulin G molecule, which are suitable for high resolution X-ray analysis, have been grown. The space group is P3121 (or enantiomorph) and the crystallographic diad relates the two halves of one molecule. 相似文献
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Marcin Wolny Melanie Colegrave Lucy Colman Ed White Peter J. Knight Michelle Peckham 《The Journal of biological chemistry》2013,288(44):31952-31962
It is unclear why mutations in the filament-forming tail of myosin heavy chain (MHC) cause hypertrophic or dilated cardiomyopathy as these mutations should not directly affect contraction. To investigate this, we first investigated the impact of five hypertrophic cardiomyopathy-causing (N1327K, E1356K, R1382W, E1555K, and R1768K) and one dilated cardiomyopathy-causing (R1500W) tail mutations on their ability to incorporate into muscle sarcomeres in vivo. We used adenoviral delivery to express full-length wild type or mutant enhanced GFP-MHC in isolated adult cardiomyocytes. Three mutations (N1327K, E1356K, and E1555K) reduced enhanced GFP-MHC incorporation into muscle sarcomeres, whereas the remainder had no effect. No mutations significantly affected contraction. Fluorescence recovery after photobleaching showed that fluorescence recovery for the mutation that incorporated least well (N1327K) was significantly faster than that of WT with half-times of 25.1 ± 1.8 and 32.2 ± 2.5 min (mean ± S.E.), respectively. Next, we determined the effects of each mutation on the helical properties of wild type and seven mutant peptides (7, 11, or 15 heptads long) from the myosin tail by circular dichroism. R1382W and E1768K slightly increased the α-helical nature of peptides. The remaining mutations reduced α-helical content, with N1327K showing the greatest reduction. Only peptides containing residues 1301–1329 were highly α-helical suggesting that this region helps in initiation of coiled coil. These results suggest that small effects of mutations on helicity translate into a reduced ability to incorporate into sarcomeres, which may elicit compensatory hypertrophy. 相似文献
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A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson's disease 下载免费PDF全文
J Carlos Villaescusa Bingsi Li Enrique M Toledo Pia Rivetti di Val Cervo Shanzheng Yang Simon RW Stott Karol Kaiser Saiful Islam Daniel Gyllborg Rocio Laguna‐Goya Michael Landreh Peter Lönnerberg Anna Falk Tomas Bergman Roger A Barker Sten Linnarsson Licia Selleri Ernest Arenas 《The EMBO journal》2016,35(18):1963-1978
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According to receptor theory, the effect of a ligand depends on the amount of agonist–receptor complex. Therefore, changes in receptor abundance should have quantitative effects. However, the response to pheromone in Saccharomyces cerevisiae is robust (unaltered) to increases or reductions in the abundance of the G‐protein‐coupled receptor (GPCR), Ste2, responding instead to the fraction of occupied receptor. We found experimentally that this robustness originates during G‐protein activation. We developed a complete mathematical model of this step, which suggested the ability to compute fractional occupancy depends on the physical interaction between the inhibitory regulator of G‐protein signaling (RGS), Sst2, and the receptor. Accordingly, replacing Sst2 by the heterologous hsRGS4, incapable of interacting with the receptor, abolished robustness. Conversely, forcing hsRGS4:Ste2 interaction restored robustness. Taken together with other results of our work, we conclude that this GPCR pathway computes fractional occupancy because ligand‐bound GPCR–RGS complexes stimulate signaling while unoccupied complexes actively inhibit it. In eukaryotes, many RGSs bind to specific GPCRs, suggesting these complexes with opposing activities also detect fraction occupancy by a ratiometric measurement. Such complexes operate as push‐pull devices, which we have recently described. 相似文献
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The effects of the carbonic anhydrase (CA) inhibitors acetazolamide (AZ) and dextran-bound sulfonamide (DBS) on HCO3 − -dependent O2 evolution in Chlorella saccharophila were evaluated. Addition of 4 μ M AZ or 0.4 mg ml−1 DBS to photosynthesizing cells reduced the O2 evolution rate at low dissolved inorganic carbon (DIC) concentration, decreased the size of the intracellular acid-labile carbon pool, and decreased the apparent affinity of the cells for DIC. Measurement of the whole-cell affinity of cells for CO2 and HCO3 − in the presence and absence of inhibitors indicated that active HCO3 − transport was inhibited by AZ and DBS. The inhibition of HCO3 − transport was independent of the inhibition of external and internal CA. These results suggest that the active uptake of HCO3 − occurs initially by the interaction of HCO3 − and a CA-like transporter. 相似文献
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We have used a (TTAGGG) oligonucleotide probe to demonstrate that ovine telomeres are composed of (TTAGGG) repeat arrays and to compare the terminal restriction fragment lengths of sheep derived by natural mating and nuclear transfer. Here we show that ovine somatic telomeres decrease in length with age, and that Dolly, derived by the transfer of 6-year-old adult somatic nucleus, exhibits diminished terminal restriction fragment lengths. The decrease is consistent with the age of the donor tissue and telomere erosion during in vitro culture. Nuclear transfer does not restore telomere lengths. Dolly otherwise appears physiologically and phenotypically normal for her breed and age. We further report on apparent telomere lengthening in sheep, occurring during the first year in naturally derived lambs. 相似文献