5 resultados para Particle and pore radii distributions
em National Center for Biotechnology Information - NCBI
Resumo:
Signal peptides direct the cotranslational targeting of nascent polypeptides to the endoplasmic reticulum (ER). It is currently believed that the signal recognition particle (SRP) mediates this targeting by first binding to signal peptides and then by directing the ribosome/nascent chain/SRP complex to the SRP receptor at the ER. We show that ribosomes can mediate targeting by directly binding to translocation sites. When purified away from cytosolic factors, including SRP and nascent-polypeptide-associated complex (NAC), in vitro assembled translation intermediates representing ribosome/nascent-chain complexes efficiently bound to microsomal membranes, and their nascent polypeptides could subsequently be efficiently translocated. Because removal of cytosolic factors from the ribosome/nascent-chain complexes also resulted in mistargeting of signalless nascent polypeptides, we previously investigated whether readdition of cytosolic factors, such as NAC and SRP, could restore fidelity to targeting. Without SRP, NAC prevented all nascent-chain-containing ribosomes from binding to the ER membrane. Furthermore, SRP prevented NAC from blocking ribosome-membrane association only when the nascent polypeptide contained a signal. Thus, NAC is a global ribosome-binding prevention factor regulated in activity by signal-peptide-directed SRP binding. A model presents ribosomes as the targeting vectors for delivering nascent polypeptides to translocation sites. In conjunction with signal peptides, SRP and NAC contribute to this specificity of ribosomal function by regulating exposure of a ribosomal membrane attachment site that binds to receptors in the ER membrane.
Resumo:
Particle candidates for astrophysical dark matter are reviewed, with particular emphasis on the lightest supersymmetric particle and the axion. The former is now constrained by accelerator experiments to have a mass above about 40 GeV, and ongoing searches at accelerators, in space, and in underground experiments have a good chance to detect it. A reevaluation of the constraint on the axion from supernova 1987a leaves open an interesting window where it may be detected if it constitutes the galactic halo.
Resumo:
A hyperphosphorylated form of the largest subunit of RNA polymerase II (pol IIo) is associated with the pre-mRNA splicing process. Pol IIo was detected in association with a subset of small nuclear ribonucleoprotein particle and Ser-Arg protein splicing factors and also with pre-mRNA splicing complexes assembled in vitro. A subpopulation of pol IIo was localized to nuclear "speckle" domains enriched in splicing factors, indicating that it may also be associated with RNA processing in vivo. Moreover, pol IIo was retained in a similar pattern following in situ extraction of cells and was quantitatively recovered in the nuclear matrix fraction. The results implicate nuclear matrix-associated hyperphosphorylated pol IIo as a possible link in the coordination of transcription and splicing processes.
Resumo:
Speech recognition involves three processes: extraction of acoustic indices from the speech signal, estimation of the probability that the observed index string was caused by a hypothesized utterance segment, and determination of the recognized utterance via a search among hypothesized alternatives. This paper is not concerned with the first process. Estimation of the probability of an index string involves a model of index production by any given utterance segment (e.g., a word). Hidden Markov models (HMMs) are used for this purpose [Makhoul, J. & Schwartz, R. (1995) Proc. Natl. Acad. Sci. USA 92, 9956-9963]. Their parameters are state transition probabilities and output probability distributions associated with the transitions. The Baum algorithm that obtains the values of these parameters from speech data via their successive reestimation will be described in this paper. The recognizer wishes to find the most probable utterance that could have caused the observed acoustic index string. That probability is the product of two factors: the probability that the utterance will produce the string and the probability that the speaker will wish to produce the utterance (the language model probability). Even if the vocabulary size is moderate, it is impossible to search for the utterance exhaustively. One practical algorithm is described [Viterbi, A. J. (1967) IEEE Trans. Inf. Theory IT-13, 260-267] that, given the index string, has a high likelihood of finding the most probable utterance.
Resumo:
We show that, after removal of the nascent polypeptide-associated complex (NAC) from ribosome-associated nascent chains, ribosomes synthesizing proteins lacking signal peptides are efficiently targeted to the endoplasmic reticulum (ER) membrane. After this mistargeting, translocation across the ER membrane occurs, albeit less efficiently than for a nascent secretory polypeptide, perhaps because the signal peptide is needed to catalyze the opening of the translocation pore. The mistargeting was prevented by the addition of purified NAC and was shown not to be mediated by the signal recognition particle and its receptor. Instead, it appears to be a consequence of the intrinsic affinity of ribosomes for membrane binding sites, since it can be blocked by competing ribosomes that lack associated nascent polypeptides. We propose that, when bound to a signalless ribosome-associated nascent polypeptide, NAC sterically blocks the site in the ribosome for membrane binding.