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Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all branches of science and how science impacts upon all aspects of society and life.
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Structural biology: Lipid gymnastics

Tue, 08/11/2015 - 23:00

Structural biology: Lipid gymnastics

Nature 524, 7566 (2015). doi:10.1038/nature15202

Authors: Alice Verchère & Anant K. Menon

Crystal structures of the bacterial protein PglK uncover structural features that suggest how the protein 'flips' lipid-bound oligosaccharide molecules from one side of the cell membrane to the other. See Article p.433

Categories: Journal Articles

Structure and mechanism of an active lipid-linked oligosaccharide flippase

Tue, 08/11/2015 - 23:00

Structure and mechanism of an active lipid-linked oligosaccharide flippase

Nature 524, 7566 (2015). doi:10.1038/nature14953

Authors: Camilo Perez, Sabina Gerber, Jérémy Boilevin, Monika Bucher, Tamis Darbre, Markus Aebi, Jean-Louis Reymond & Kaspar P. Locher

The flipping of membrane-embedded lipids containing large, polar head groups is slow and energetically unfavourable, and is therefore catalysed by flippases, the mechanisms of which are unknown. A prominent example of a flipping reaction is the translocation of lipid-linked oligosaccharides that serve as donors in

Categories: Journal Articles

SEC14L2 enables pan-genotype HCV replication in cell culture

Tue, 08/11/2015 - 23:00

SEC14L2 enables pan-genotype HCV replication in cell culture

Nature 524, 7566 (2015). doi:10.1038/nature14899

Authors: Mohsan Saeed, Ursula Andreo, Hyo-Young Chung, Christine Espiritu, Andrea D. Branch, Jose M. Silva & Charles M. Rice

Since its discovery in 1989, efforts to grow clinical isolates of the hepatitis C virus (HCV) in cell culture have met with limited success. Only the JFH-1 isolate has the capacity to replicate efficiently in cultured hepatoma cells without cell culture-adaptive mutations. We hypothesized that cultured cells lack one or more factors required for the replication of clinical isolates. To identify the missing factors, we transduced Huh-7.5 human hepatoma cells with a pooled lentivirus-based human complementary DNA (cDNA) library, transfected the cells with HCV subgenomic replicons lacking adaptive mutations, and selected for stable replicon colonies. This led to the identification of a single cDNA, SEC14L2, that enabled RNA replication of diverse HCV genotypes in several hepatoma cell lines. This effect was dose-dependent, and required the continuous presence of SEC14L2. Full-length HCV genomes also replicated and produced low levels of infectious virus. Remarkably, SEC14L2-expressing Huh-7.5 cells also supported HCV replication following inoculation with patient sera. Mechanistic studies suggest that SEC14L2 promotes HCV infection by enhancing vitamin E-mediated protection against lipid peroxidation. This provides a foundation for development of in vitro replication systems for all HCV isolates, creating a useful platform to dissect the mechanisms by which cell culture-adaptive mutations act.

Categories: Journal Articles