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121.
Mareuil F Sizun C Perez J Schoenauer M Lallemand JY Bontems F 《European biophysics journal : EBJ》2007,37(1):95-104
Most proteins comprise several domains and/or participate in functional complexes. Owing to ongoing structural genomic projects,
it is likely that it will soon be possible to predict, with reasonable accuracy, the conserved regions of most structural
domains. Under these circumstances, it will be important to have methods, based on simple-to-acquire experimental data, that
allow to build and refine structures of multi-domain proteins or of protein complexes from homology models of the individual
domains/proteins. It has been recently shown that small angle X-ray scattering (SAXS) and NMR residual dipolar coupling (RDC)
data can be combined to determine the architecture of such objects when the X-ray structures of the domains are known and
can be considered as rigid objects. We developed a simple genetic algorithm to achieve the same goal, but by using homology
models of the domains considered as deformable objects. We applied it to two model systems, an S1KH bi-domain of the NusA
protein and the γS-crystallin protein. Despite its simplicity our algorithm is able to generate good solutions when driven
by SAXS and RDC data. 相似文献
122.
123.
Holterman CE Le Grand F Kuang S Seale P Rudnicki MA 《The Journal of cell biology》2007,179(5):911-922
We identify here the multiple epidermal growth factor repeat transmembrane protein Megf10 as a quiescent satellite cell marker that is also expressed in skeletal myoblasts but not in differentiated myofibers. Retroviral expression of Megf10 in myoblasts results in enhanced proliferation and inhibited differentiation. Infected myoblasts that fail to differentiate undergo cell cycle arrest and can reenter the cell cycle upon serum restimulation. Moreover, experimental modulations of Megf10 alter the expression levels of Pax7 and the myogenic regulatory factors. In contrast, Megf10 silencing in activated satellite cells on individual fibers or in cultured myoblasts results in a dramatic reduction in the cell number, caused by myogenin activation and precocious differentiation as well as a depletion of the self-renewing Pax7+/MyoD− population. Additionally, Megf10 silencing in MyoD−/− myoblasts results in down-regulation of Notch signaling components. We conclude that Megf10 represents a novel transmembrane protein that impinges on Notch signaling to regulate the satellite cell population balance between proliferation and differentiation. 相似文献
124.
Sol-Foulon N Sourisseau M Porrot F Thoulouze MI Trouillet C Nobile C Blanchet F di Bartolo V Noraz N Taylor N Alcover A Hivroz C Schwartz O 《The EMBO journal》2007,26(2):516-526
HIV efficiently spreads in lymphocytes, likely through virological synapses (VSs). These cell-cell junctions share some characteristics with immunological synapses, but cellular proteins required for their constitution remain poorly characterized. We have examined here the role of ZAP-70, a key kinase regulating T-cell activation and immunological synapse formation, in HIV replication. In lymphocytes deficient for ZAP-70, or expressing a kinase-dead mutant of the protein, HIV replication was strikingly delayed. We have characterized further this replication defect. ZAP-70 was dispensable for the early steps of viral cycle, from entry to expression of viral proteins. However, in the absence of ZAP-70, intracellular Gag localization was impaired. ZAP-70 was required in infected donor cells for efficient cell-to-cell HIV transmission to recipients and for formation of VSs. These results bring novel insights into the links that exist between T-cell activation and HIV spread, and suggest that HIV usurps components of the immunological synapse machinery to ensure its own spread through cell-to-cell contacts. 相似文献
125.
Massip L Ectors F Deprez P Maleki M Behets C Lengelé B Delahaut P Picard J Rezsöhazy R 《Differentiation; research in biological diversity》2007,75(3):256-267
Vertebrate Hox genes act as developmental architects by patterning embryonic structures like axial skeletal elements, limbs, brainstem territories, or neural crest derivatives. While active during the patterning steps of development, these genes turn out to be down-regulated in specific differentiation programs like that leading to chondrogenesis. To investigate why chondrocyte differentiation is correlated to the silencing of a Hox gene, we generated transgenic mice allowing Cre-mediated conditional misexpression of Hoxa2 and induced this gene in Collagen 2 alpha 1-expressing cells committed to enter chondrogenesis. Persistent Hoxa2 expression in chondrogenic cells resulted in overall chondrodysplasia with delayed cartilage hypertrophy, mineralization, and ossification but without proliferation defects. The absence of skeletal patterning anomaly and the regular migration of precursor cells indicated that the condensation step of chondrogenesis was normal. In contrast, closer examination at the differentiation step showed severely impaired chondrocyte differentiation. In addition, this inhibition affected structures independently of their embryonic origin. In conclusion, for the first time here, by a cell-type specific misexpression, we precisely uncoupled the patterning function of Hoxa2 from its involvement in regulating differentiation programs per se and demonstrate that Hoxa2 displays an anti-chondrogenic activity that is distinct from its patterning function. 相似文献
126.
Transition metal ions are required for many aspects of mitochondrial physiology. Copper, iron, manganese and zinc are cofactors
in metalloenzymes and metalloproteins within the organelle. Little is known how cells maintain optimal pools of these metal
ions for mitochondrial function. This review documents the available literature on mitochondrial metal ion pools and protein
metallation reactions. Upon perturbation in metal pools, mis-metallation reactions do occur. Thus, regulation of metal ion
accessibility and bioavailability must exist. 相似文献
127.
Chopin F Orsel M Dorbe MF Chardon F Truong HN Miller AJ Krapp A Daniel-Vedele F 《The Plant cell》2007,19(5):1590-1602
In higher plants, nitrate is taken up by root cells where Arabidopsis thaliana NITRATE TRANSPORTER2.1 (ATNRT2.1) chiefly acts as the high-affinity nitrate uptake system. Nitrate taken up by the roots can then be translocated from the root to the leaves and the seeds. In this work, the function of the ATNRT2.7 gene, one of the seven members of the NRT2 family in Arabidopsis, was investigated. High expression of the gene was detected in reproductive organs and peaked in dry seeds. beta-Glucuronidase or green fluorescent protein reporter gene expression driven by the ATNRT2.7 promoter confirmed this organ specificity. We assessed the capacity of ATNRT2.7 to transport nitrate in Xenopus laevis oocytes or when it is expressed ectopically in mutant plants deficient in nitrate transport. We measured the impact of an ATNRT2.7 mutation and found no difference from the wild type during vegetative development. By contrast, seed nitrate content was affected by overexpression of ATNRT2.7 or a mutation in the gene. Finally, we showed that this nitrate transporter protein was localized to the vacuolar membrane. Our results demonstrate that ATNRT2.7 plays a specific role in nitrate accumulation in the seed. 相似文献
128.
MOTIVATION: Experimentalists have amassed extensive evidence over the past four decades that proteins appear to fold during production by the ribosome. Protein structure prediction methods, however, do not incorporate this property of folding. A thorough study to find the fingerprint of such sequential folding is the first step towards using it in folding algorithms, so assisting structure prediction. RESULTS: We explore computationally the existence of evidence for cotranslational folding, based on large sets of experimentally determined structures in the PDB. Our perspective is that cotranslational folding is the norm, but that the effect is masked in most classes. We show that it is most evident in alpha/beta proteins, confirming recent findings. We also find mild evidence that older proteins may fold cotranslationally. A tool is provided for determining, within a protein, where cotranslation is most evident. 相似文献
129.
James FO Boivin DB Charbonneau S Bélanger V Cermakian N 《Chronobiology international》2007,24(6):1009-1034
The rhythmic expression of circadian clock genes in the neurons of the suprachiasmatic nucleus (SCN) underlies the manifestation of endogenous circadian rhythmicity in behavior and physiology. Recent evidence demonstrating rhythmic clock gene expression in non-SCN tissues suggests that functional clocks exist outside the central circadian pacemaker of the brain. In this investigation, the nature of an oscillator in peripheral blood mononuclear cells (PBMCs) is evaluated by assessing clock gene expression throughout both a typical sleep/wake cycle (LD) and during a constant routine (CR). Six healthy men and women aged (mean±SEM) 23.7±1.6 yrs participated in this five-day investigation in temporal isolation. Core body temperature and plasma melatonin concentration were measured as markers of the central circadian pacemaker. The expression of HPER1, HPER2, and HBMAL1 was quantified in PBMCs sampled throughout an uninterrupted 72 h period. The core body temperature minimum and the midpoint of melatonin concentration measured during the CR occurred 2:17±0:20 and 3:24 ±0:09 h before habitual awakening, respectively, and were well aligned to the sleep/wake cycle. HPER1 and HPER2 expression in PBMCs demonstrated significant circadian rhythmicity that peaked early after wake-time and was comparable under LD and CR conditions. HBMAL1 expression was more variable, and peaked in the middle of the wake period under LD conditions and during the habitual sleep period under CR conditions. For the first time, bi-hourly sampling over three consecutive days is used to compare clock gene expression in a human peripheral oscillator under different sleep/wake conditions. 相似文献
130.
Satellite and stem cells in muscle growth and repair 总被引:2,自引:0,他引:2
The FASEB summer research conference on Skeletal Muscle Satellite and Stem Cells, organized by Thomas Rando, Giulio Cossu and Jeffrey Chamberlain, was held in Indian Wells, California, in July. An international array of researchers gathered to share numerous new insights into the cellular and molecular regulation of stem cells and satellite cells in skeletal muscle biology. The conference is unique in that it brings together investigators from diverse backgrounds, who work on the growth and repair of skeletal muscle in humans and model systems, in health and disease. 相似文献