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81.
Morgan DG Ménétret JF Neuhof A Rapoport TA Akey CW 《Journal of molecular biology》2002,324(4):871-886
The co-translational translocation of proteins into the endoplasmic reticulum (ER) lumen and the biogenesis of membrane proteins require ribosome binding to a membrane channel formed by the Sec61p complex. We now report the 17A structure of a mammalian ribosome-channel complex derived from ER membranes. Atomic models of the ribosomal subunits were aligned to the programmed ribosome from Thermus thermophilus, to provide a common reference frame. The T.thermophilus ribosome, and by extension all known high resolution subunit models, were then docked within our map of the ribosome-channel complex. The structure shows that the ribosome contains a putative tRNA in the exit site, and a comparison with a non-programmed, yeast ribosome suggests that the L1 stalk may function as a gate in the tRNA exit path. We have localized six major expansion segments in the large subunit of the vertebrate ribosome including ES27, and suggest a function for ES30.The large ribosomal subunit is linked to the channel by four connections. We identified regions in the large subunit rRNA and four proteins that may help form the connections. These regions of the ribosome probably serve as a template to guide the assembly of the asymmetric translocation channel. Three of the connections form a picket fence that separates the putative translocation pore from the attachment site of an additional membrane component. The ribosome-channel connections also create an open junction that would allow egress of a nascent chain into the cytosol. At a threshold that is appropriate for the entire complex, the channel is rather solid and the lumenal half of the putative translocation pore is closed. These data suggest that the flow of small molecules across the membrane may be impeded by the channel itself, rather than the ribosome-channel junction. 相似文献
82.
Boll W Rapoport I Brunner C Modis Y Prehn S Kirchhausen T 《Traffic (Copenhagen, Denmark)》2002,3(8):590-600
The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. We have used a combination of surface plasmon resonance and crosslinking with a photoactivated peptide probe to demonstrate the interaction between FDNPVY-containing peptides and the μ2 chain of purified AP-2 clathrin adaptors (the complexes responsible for plasma membrane sorting). We show that recognition of the FDNPVY signal is mediated by a binding site in the μ2-subunit that is distinct from the site for the more general YppØ sorting signal, another tyrosine-based sequence also recognized by μ2-adaptin. These results suggest the possibility that low-density lipoprotein receptor uptake may be modulated specifically and independently of other proteins in the clathrin pathway. 相似文献
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Flitman-Tene R Levisohn S Lysnyansky I Rapoport E Yogev D 《FEMS microbiology letters》2000,191(2):205-212
A Mycoplasma agalactiae genomic fragment carrying four vsp-related genes (designated avg: agalactiae variable genes) was cloned, sequenced and compared to the vspA gene of Mycoplasma bovis. The following features were revealed: (i) the presence of a highly conserved vsp 5' upstream region; (ii) a highly homologous vsp N-terminal end encoding a putative lipoprotein signal sequence; (iii) sequence divergence of the rest of the mature proteins. By using avg specific probes in Southern blot analysis of genomic DNAs of M. agalactiae strains as well as of isolates from infected animals, marked DNA polymorphism of avg fragments was demonstrated. In addition, the avg genomic fingerprints were monitored for a period of 7 months, in isolates of M. agalactiae from an individual chronically infected animal. The results provided evidence that a chromosomal region of M. agalactiae, carrying vsp-related genes, undergoes rearrangements in vivo in the natural animal host during the course of infection. 相似文献
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Summary The fine structural features of cultured PC12 cells were investigated after treatment for 1, 3, or 5 days with different concentrations of the vascular form of β- 1–40 (β-AP). PC12 cells treated with β-AP showed time- and concentration-dependent lysosomal system activation and cell toxicity. We observed increases in the number and size of cytoplasmic lysosomes as indicated by increased acid phosphatase reactivity. Some lysosomes were in the form of multivesicular bodies or large residual bodies that appeared to arise by autophagia or by endocytotic uptake. Double-sided plasma membrane invaginations were observed to give rise to increasingly extensive intracytoplasmic vacuolization that was correlated with duration of β-AP treatment. Freeze-fracture studies of the intramembranous particle (IMP) population in the plasma membrane P-face showed that both control and β-AP treated cells had two major P-face IMP populations, small-diameter (4–8 nm) IMPs, and large-diameter (≤ 9nm) IMPs. The larger category of IMPs was found to possess a greater average diameter in the β-AP treated cells than in the control cells. These IMPs could represent modifications to existing transmembranous receptors, channels, or transducing molecules by the β-AP. These results demonstrate that β-AP can induce time- and concentration-dependent ultrastructural changes in PC12 cell membranes. 相似文献
90.
Mechanisms determining the morphology of the peripheral ER 总被引:1,自引:0,他引:1
The endoplasmic reticulum (ER) consists of the nuclear envelope and a peripheral network of tubules and membrane sheets. The tubules are shaped by the curvature-stabilizing proteins reticulons and DP1/Yop1p, but how the sheets are formed is unclear. Here, we identify several sheet-enriched membrane proteins in the mammalian ER, including proteins that translocate and modify newly synthesized polypeptides, as well as coiled-coil membrane proteins that are highly upregulated in cells with proliferated ER sheets, all of which are localized by membrane-bound polysomes. These results indicate that sheets and tubules correspond to rough and smooth ER, respectively. One of the coiled-coil proteins, Climp63, serves as a "luminal ER spacer" and forms sheets when overexpressed. More universally, however, sheet formation appears to involve the reticulons and DP1/Yop1p, which localize to sheet edges and whose abundance determines the ratio of sheets to tubules. These proteins may generate sheets by stabilizing the high curvature of edges. 相似文献