Catálogo de publicaciones - revistas

<jats:title>Dissecting Hippo Interactions</jats:title> <jats:p> The Hippo signaling pathway plays key roles in many processes, from cell proliferation and cell death to regulation of stem cells and cancer cells. <jats:bold> Kwon <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="737" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1243971">737</jats:related-article> , published 10 October) attempted to systematically identify all components of the pathway. A protein-protein interaction screen identified more than 200 interactions among approximately 150 proteins. A protein identified in the screen, Leash, restrained the activity of the transcriptional coactivator Yorkie, which regulates gene expression in response to Hippo signaling. </jats:p>

<jats:title>Bridging the Titin Gap</jats:title> <jats:p> The muscle protein titin is a molecular spring that has been extensively studied by single-molecule unfolding experiments and by molecular simulation. However, experimental and simulated unfolding could not be compared directly because they differ by orders of magnitude in pulling velocity. <jats:bold> Rico <jats:italic>et al.</jats:italic> </jats:bold> (p <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="741" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1239764">741</jats:related-article> ) developed high-speed force spectroscopy to pull titin molecules at speeds that reach the lower limits of molecular dynamics simulations. Bridging the gap between simulation and experiment clarified the mechanism of conformational changes in titin. </jats:p>

<jats:title>DNA Differences</jats:title> <jats:p> The extent to which genetic variation affects an individual's phenotype has been difficult to predict because the majority of variation lies outside the coding regions of genes. Now, three studies examine the extent to which genetic variation affects the chromatin of individuals with diverse ancestry and genetic variation (see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="705" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1246755"> <jats:bold>Furey and Sethupathy</jats:bold> </jats:related-article> ). <jats:bold> Kasowski <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="750" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1242510">750</jats:related-article> , published online 17 October) examined how genetic variation affects differences in chromatin states and their correlation to histone modifications, as well as more general DNA binding factors. <jats:bold> Kilpinen <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="744" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1242463">744</jats:related-article> , published online 17 October) document how genetic variation is linked to allelic specificity in transcription factor binding, histone modifications, and transcription. <jats:bold> McVicker <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="747" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1242429">747</jats:related-article> , published online 17 October) identified how quantitative trait loci affect histone modifications in Yoruban individuals and established which specific transcription factors affect such modifications. </jats:p>

<jats:title>DNA Differences</jats:title> <jats:p> The extent to which genetic variation affects an individual's phenotype has been difficult to predict because the majority of variation lies outside the coding regions of genes. Now, three studies examine the extent to which genetic variation affects the chromatin of individuals with diverse ancestry and genetic variation (see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="705" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1246755"> <jats:bold>Furey and Sethupathy</jats:bold> </jats:related-article> ). <jats:bold> Kasowski <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="750" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1242510">750</jats:related-article> , published online 17 October) examined how genetic variation affects differences in chromatin states and their correlation to histone modifications, as well as more general DNA binding factors. <jats:bold> Kilpinen <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="744" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1242463">744</jats:related-article> , published online 17 October) document how genetic variation is linked to allelic specificity in transcription factor binding, histone modifications, and transcription. <jats:bold> McVicker <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="747" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1242429">747</jats:related-article> , published online 17 October) identified how quantitative trait loci affect histone modifications in Yoruban individuals and established which specific transcription factors affect such modifications. </jats:p>

<jats:title>DNA Differences</jats:title> <jats:p> The extent to which genetic variation affects an individual's phenotype has been difficult to predict because the majority of variation lies outside the coding regions of genes. Now, three studies examine the extent to which genetic variation affects the chromatin of individuals with diverse ancestry and genetic variation (see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="705" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1246755"> <jats:bold>Furey and Sethupathy</jats:bold> </jats:related-article> ). <jats:bold> Kasowski <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="750" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1242510">750</jats:related-article> , published online 17 October) examined how genetic variation affects differences in chromatin states and their correlation to histone modifications, as well as more general DNA binding factors. <jats:bold> Kilpinen <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="744" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1242463">744</jats:related-article> , published online 17 October) document how genetic variation is linked to allelic specificity in transcription factor binding, histone modifications, and transcription. <jats:bold> McVicker <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6159" page="747" related-article-type="in-this-issue" vol="342" xlink:href="10.1126/science.1242429">747</jats:related-article> , published online 17 October) identified how quantitative trait loci affect histone modifications in Yoruban individuals and established which specific transcription factors affect such modifications. </jats:p>

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<jats:title>Dead Wood</jats:title> <jats:p> Trees can be affected by a wide variety of diseases caused by insects, fungi, and other pathogens. Such diseases often make the headlines—particularly when iconic tree species are affected—for example, in the case of the ash dieback currently spreading through Europe, or the chestnut blight that devastated American chestnut trees. But what is the effect of these diseases on ecosystem services performed by trees in natural and managed ecosystems? <jats:bold> Boyd <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" related-article-type="in-this-issue" xlink:href="10.1126/science.1235773">10.1126/science.1235773</jats:related-article> ) review the spread of tree diseases, as a result of globalization and climate change, and analyze the resulting damage to timber and fruit production, to climate regulation, and to parks and woodlands caused by tree diseases. </jats:p>

<jats:sec> <jats:title /> <jats:sec> <jats:title>Introduction</jats:title> <jats:p> Initiation of protein synthesis is a key step in the control of gene expression. In eukaryotes, initiation is a highly complex process that requires almost a dozen protein factors. The last step involves joining of the large and small subunits of the ribosome to form the 80 <jats:italic>S</jats:italic> initiation complex with the transfer RNA (tRNA) in the P-site base paired to the start codon. This step is catalyzed by the guanosine triphosphatase (GTPase) factor eIF5B. In addition, eIF5B is thought to play a role in ensuring that translation initiation takes place only on mature ribosomes. </jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>The development of fast, direct electron detectors and new methods of image analysis for cryo–electron microscopy allow high-resolution reconstructions from much smaller numbers of particles than previously possible. We used these new methods to provide feedback to improve the biochemical preparation of samples for structure determination of the eukaryotic translation initiation complex with initiator tRNA and eIF5B, which was trapped on the ribosome with the nonhydrolyzable GTP analog GDPCP.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Although the structure of the fully assembled complex was calculated from only 5143 particles, representing just 3% of the population in the sample, it was possible to obtain a resolution of 6.6 Å. This allowed us to propose a molecular model for the initiation complex. The structure shows that the subunits of the ribosome are rotated relative to the canonical state after initiation. The long helix and C-terminal domain of eIF5B have changed conformation and moved into the ribosome, where the C-terminal domain interacts with the initiator tRNA. The tRNA is stabilized in a distorted conformation, with its 3′-CCA end out of the peptidyl transferase center.</jats:p> </jats:sec> <jats:sec> <jats:title>Discussion</jats:title> <jats:p> The conformational change in eIF5B may be induced upon binding to the small (40 <jats:italic>S</jats:italic> ) subunit when it specifically recognizes initiator tRNA. In its altered conformation, eIF5B interacts simultaneously with the initiator tRNA and the GTPase center of the ribosome, thus coupling GTP hydrolysis with tRNA recognition in the ribosome. The large number of contacts made by eIF5B with the ribosomal subunits and tRNA is consistent with its role in subunit joining. A close contact with the eukaryote-specific ribosomal protein L40 would not be possible in the immature ubiquitinated form of L40, thus precluding the recruitment of immature 60 <jats:italic>S</jats:italic> subunits. A comparison with previous work on the bacterial homolog IF2 suggests that the mechanism of this step of initiation is conserved across kingdoms. Finally, the use of recent advances in cryo-EM to determine a relatively high-resolution structure of the eIF5B-ribosome complex from a very small fraction of a sample could be a general approach for the study of other dynamic or transient biological complexes. </jats:p> </jats:sec> </jats:sec>