Catálogo de publicaciones - revistas

<jats:title>Clustering for the kill</jats:title> <jats:p> Cluster of differentiation 20 (CD20) is a membrane protein that defines most B cell populations and is the target of therapeutic antibodies to treat malignancies and autoimmune disorders. Rougé <jats:italic>et al.</jats:italic> present the structure of CD20 bound to the antibody rituximab that activates the complement system to kill B cells. CD20 forms a dimer and each monomer binds one rituximab antigen-binding fragment (Fab) to give 2:2 stoichiometry. The compact packing between Fab arms and CD20 gives rise to circular assemblies with a diameter similar to that of antibody hexamers known to recruit the first component of the complement cascade. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6483" page="1224" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aaz9356">1224</jats:related-article> </jats:p>

<jats:title>How amyloid can be a substrate of memory</jats:title> <jats:p> Formation of memories requires changes in the molecular composition of the synapse. How these changes occur and what maintains this altered synaptic composition so that memory can persist are unknown. Hervas <jats:italic>et al.</jats:italic> report the structure of a synaptic translation regulator called Orb2 isolated from the brains of adult fruit flies that is important for the maintenance and recall of memory. Orb2 forms an amyloid and changes its activity from a translation repressor to an activator. The amyloid core is composed of polar hydrophilic residues, as opposed to the hydrophobic ones found in nonfunctional or pathological amyloids. The structure provides insights into how amyloids could be a stable yet malleable substrate of memory. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6483" page="1230" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aba3526">1230</jats:related-article> </jats:p>

<jats:title>An underground record of past deglaciations</jats:title> <jats:p> Understanding more exactly how the timing of deglaciations depends on changes in insolation, or the energy received by Earth from the Sun, requires precise and independent records of both environmental change and solar energy input. Bajo <jats:italic>et al</jats:italic> . strengthened the weak link of that two-member chain, the environmental record, by developing a precise, radiometrically dated chronology of the 11 deglaciations of the past million years derived from speleothems. This allowed them to show more clearly how the initiation and duration of glacial terminations over that period depended on solar obliquity and precession. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6483" page="1235" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aaw1114">1235</jats:related-article> </jats:p>

<jats:title>Snapshots of a rotary pump</jats:title> <jats:p> Vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases) are ATP-hydrolysis–driven proton pumps. In neurons, V-ATPase activity generates a proton gradient across the membrane of synaptic vesicles so that neurotransmitters can be loaded into the vesicles. Abbas <jats:italic>et al.</jats:italic> developed a method to purify V-ATPase from rat brain and determined the structure of the entire complex by cryo–electron microscopy. Native mass spectrometry showed that the preparation was homogeneous and complemented structural studies by confirming the subunit composition. Three rotational states were resolved at better than 4-angstrom resolution, providing insight into the conformational changes that couple ATP hydrolysis to proton pumping. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6483" page="1240" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aaz2924">1240</jats:related-article> </jats:p>

<jats:title>Asymmetry on the plus side</jats:title> <jats:p> Numerous positively charged metal catalysts have been paired with chiral negative ions to select for just one of two mirror-image products. Genov <jats:italic>et al.</jats:italic> now report a potentially general strategy to invert the charges in this paradigm. Because intrinsically negative metal catalysts are comparatively rare, the authors appended a sulfonate group to the common bipyridyl ligand. Iridium complexes of this ligand paired with chiral positive ions could borylate just one of two aryl rings appended to carbon or phosphorus centers with high enantioselectivity. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6483" page="1246" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aba1120">1246</jats:related-article> </jats:p>

<jats:title>Evaporating futures</jats:title> <jats:p>Drought and warming have been shrinking Colorado River flow for many years. Milly and Dunne used a hydrologic model and historical observations to show that this decrease is due mainly to increased evapotranspiration caused by a reduction of albedo from snow loss and the associated rise in the absorption of solar radiation (see the Perspective by Hobbins and Barsugli). This drying will be greater than the projected precipitation increases expected from climate warming, increasing the risk of severe water shortages in an already vulnerable region.</jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6483" page="1252" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aay9187">1252</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6483" page="1192" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.abb3624">1192</jats:related-article> </jats:p>

<jats:title>Deadenylate or activate?</jats:title> <jats:p> When cells are quiescent, they undergo reversible cell cycle arrest and evince low basal metabolism. Naïve T cells are normally quiescent until they recognize cognate antigens through T cell receptor–costimulatory molecule signaling. T cell quiescence appears to be an active process, but the mechanistic details are poorly understood. Hwang <jats:italic>et al.</jats:italic> report that the transcription factors BTG1 and BTG2 are selectively expressed in quiescent T cells. In mice, T cells conditionally knocked out for both factors showed enhanced proliferation and a lowered threshold of activation both in vitro and in response to <jats:italic>Listeria monocytogenes</jats:italic> infection. Deficiency of BTG1 and BTG2 resulted in increases in global messenger RNA half-life, suggesting that messenger RNA deadenylation and degradation are important processes for maintaining T cell quiescence. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6483" page="1255" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aax0194">1255</jats:related-article> </jats:p>

<jats:title>Structure of the nCoV trimeric spike</jats:title> <jats:p> The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp <jats:italic>et al.</jats:italic> determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6483" page="1260" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.abb2507">1260</jats:related-article> </jats:p>

<jats:title>Cancer drivers converge on NOTCH</jats:title> <jats:p> Cancer genome–sequencing projects have emphasized the handful of genes mutated at high frequency in patients. Less attention has been directed to the hundreds of genes mutated in only a few patients—the so-called “long tail” mutations. Although rare, these mutations may nonetheless inform patient care. Loganathan <jats:italic>et al.</jats:italic> developed a reverse genetic CRISPR screen that allowed them to functionally assess in mice nearly 500 long tail gene mutations that occur in human head and neck squamous cell carcinoma (HNSCC). They identified 15 tumor-suppressor genes with activities that converged on the NOTCH signaling pathway. Given that NOTCH itself is mutated at high frequency in HNSCC, these results suggest that the growth of these tumors is largely driven by NOTCH inactivation. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6483" page="1264" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aax0902">1264</jats:related-article> </jats:p>