Nature Structural & Molecular Biology
Papers 5682
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The first structure of this unusual recombinase in complex with substrate DNAs reveals surprisingly unpaired and refolded transposon end DNAs that are positioned in part by direct interactions with a GTP cofactor.
#1George Ghanim (University of California, Berkeley)
#2Elizabeth H. Kellogg (California Institute for Quantitative Biosciences)
Last.Donald C. Rio (University of California, Berkeley)H-Index: 41
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P element transposase catalyzes the mobility of P element DNA transposons within the Drosophila genome. P element transposase exhibits several unique properties, including the requirement for a guanosine triphosphate cofactor and the generation of long staggered DNA breaks during transposition. To gain insights into these features, we determined the atomic structure of the Drosophila P element transposase strand transfer complex using cryo-EM. The structure of this post-transposition nucleoprote...
#1Appu K. Singh (Columbia University)H-Index: 9
#2L.L. McGoldrick (Columbia University)H-Index: 4
Last.Alexander I. Sobolevsky (Columbia University)H-Index: 25
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We present structures of mouse TRPV3 in temperature-dependent open, closed and intermediate states that suggest two-step activation of TRPV3 by heat. During the strongly temperature-dependent first step, sensitization, the channel pore remains closed while S6 helices undergo α-to-π transitions. During the weakly temperature-dependent second step, channel opening, tight association of the S1–S4 and pore domains is stabilized by changes in the carboxy-terminal and linker domains. Cryo-EM structure...
#1Aliaksandra Radzisheuskaya (UCPH: University of Copenhagen)
#2Pavel V. Shliaha (University of Southern Denmark)H-Index: 8
Last.Kristian Helin (UCPH: University of Copenhagen)H-Index: 96
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Protein arginine methyltransferase 5 (PRMT5) has emerged as a promising cancer drug target, and three PRMT5 inhibitors are currently in clinical trials for multiple malignancies. In this study, we investigated the role of PRMT5 in human acute myeloid leukemia (AML). Using an enzymatic dead version of PRMT5 and a PRMT5-specific inhibitor, we demonstrated the requirement of the catalytic activity of PRMT5 for the survival of AML cells. We then identified PRMT5 substrates using multiplexed quantita...
#1H.V. Dang (UW: University of Washington)
#2Yee-Peng Chan (USU: Uniformed Services University of the Health Sciences)H-Index: 13
Last.David Veesler (UW: University of Washington)H-Index: 24
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Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50–100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanizat...
#1Rinku Jain (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 14
#2William J. RiceH-Index: 16
Last.Aneel K. Aggarwal (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 52
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DNA polymerase δ (Polδ) plays pivotal roles in eukaryotic DNA replication and repair. Polδ is conserved from yeast to humans, and mutations in human Polδ have been implicated in various cancers. Saccharomyces cerevisiae Polδ consists of catalytic Pol3 and the regulatory Pol31 and Pol32 subunits. Here, we present the near atomic resolution (3.2 A) cryo-EM structure of yeast Polδ holoenzyme in the act of DNA synthesis. The structure reveals an unexpected arrangement in which the regulatory subunit...
#1Qiang Wang (UCSF: University of California, San Francisco)H-Index: 3
#2Shingo Kajimura (UCSF: University of California, San Francisco)H-Index: 43
Beige fat serves as a substantial metabolic sink that dissipates energy and has consequently attracted much attention as a target for improving metabolic health. A recent study has provided a new molecular target, the N-terminal acetyltransferase Naa10p, for harnessing beige-fat biogenesis and improving whole-body energy homeostasis1.
#1S. Cho (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 2
#2Rosanna P. Baker (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 9
Last.Sinisa Urban (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 26
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Protein cleavage inside the cell membrane triggers various pathophysiological signaling pathways, but the mechanism of catalysis is poorly understood. We solved ten structures of the Escherichia coli rhomboid protease in a bicelle membrane undergoing time-resolved steps that encompass the entire proteolytic reaction on a transmembrane substrate and an aldehyde inhibitor. Extensive gate opening accompanied substrate, but not inhibitor, binding, revealing that substrates and inhibitors take differ...
#1Manuel Beltran (UCL: University College London)H-Index: 5
#2Manuel Tavares (UCL: University College London)H-Index: 1
Last.Richard G. Jenner (UCL: University College London)H-Index: 24
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Polycomb repressive complex 2 (PRC2) maintains repression of cell-type-specific genes but also associates with genes ectopically in cancer. While it is currently unknown how PRC2 is removed from genes, such knowledge would be useful for the targeted reversal of deleterious PRC2 recruitment events. Here, we show that G-tract RNA specifically removes PRC2 from genes in human and mouse cells. PRC2 preferentially binds G tracts within nascent precursor mRNA (pre-mRNA), especially within predicted G-...