Category Archives: Cell

Related Articles
Common Disease Is More Complex Than Implied by the Core Gene Omnigenic Model.
Cell. 2018 Jun 14;173(7):1573-1580
Authors: Wray NR, Wijmenga C, Sullivan PF, Yang J, Visscher PM
Abstract
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Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress.

Cell. 2015 Nov 6;

Authors: Fox JM, Long F, Edeling MA, Lin H, van Duijl-Richter MK, Fong RH, Kahle KM, Smit JM, Jin J, Simmons G, Doranz BJ, Crowe JE, Fremont DH, Rossmann MG, Diamond MS

Abstract
We screened a panel of mouse and human monoclonal antibodies (MAbs) against chikungunya virus and identified several with inhibitory activity against multiple alphaviruses. Passive transfer of broadly neutralizing MAbs protected mice against infection by chikungunya, Mayaro, and O’nyong’nyong alphaviruses. Using alanine-scanning mutagenesis, loss-of-function recombinant proteins and viruses, and multiple functional assays, we determined that broadly neutralizing MAbs block multiple steps in the viral lifecycle, including entry and egress, and bind to a conserved epitope on the B domain of the E2 glycoprotein. A 16 Å resolution cryo-electron microscopy structure of a Fab fragment bound to CHIKV E2 B domain provided an explanation for its neutralizing activity. Binding to the B domain was associated with repositioning of the A domain of E2 that enabled cross-linking of neighboring spikes. Our results suggest that B domain antigenic determinants could be targeted for vaccine or antibody therapeutic development against multiple alphaviruses of global concern.

PMID: 26553503 [PubMed – as supplied by publisher]

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Insights into Secondary Metabolism from a Global Analysis of Prokaryotic Biosynthetic Gene Clusters.

Cell. 2014 Jul 17;158(2):412-421

Authors: Cimermancic P, Medema MH, Claesen J, Kurita K, Wieland Brown LC, Mavrommatis K, Pati A, Godfrey PA, Koehrsen M, Clardy J, Birren BW, Takano E, Sali A, Linington RG, Fischbach MA

Abstract
Although biosynthetic gene clusters (BGCs) have been discovered for hundreds of bacterial metabolites, our knowledge of their diversity remains limited. Here, we used a novel algorithm to systematically identify BGCs in the extensive extant microbial sequencing data. Network analysis of the predicted BGCs revealed large gene cluster families, the vast majority uncharacterized. We experimentally characterized the most prominent family, consisting of two subfamilies of hundreds of BGCs distributed throughout the Proteobacteria; their products are aryl polyenes, lipids with an aryl head group conjugated to a polyene tail. We identified a distant relationship to a third subfamily of aryl polyene BGCs, and together the three subfamilies represent the largest known family of biosynthetic gene clusters, with more than 1,000 members. Although these clusters are widely divergent in sequence, their small molecule products are remarkably conserved, indicating for the first time the important roles these compounds play in Gram-negative cell biology.

PMID: 25036635 [PubMed – as supplied by publisher]

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Related Articles
Antibiotic-induced replication stress triggers bacterial competence by increasing gene dosage near the origin.
Cell. 2014 Apr 10;157(2):395-406
Authors: Slager J, Kjos M, Attaiech L, Veening JW
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