| 1. |
- Hällberg, B Martin, et al.
(författare)
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TFAM forces mtDNA to make a U-turn
- 2011
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Ingår i: Nature Structural and Molecular Biology. - Stockholm : Karolinska Institutet, Dept of Cell and Molecular Biology. - 1545-9993 .- 1545-9985.
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Tidskriftsartikel (refereegranskat)abstract
- The mammalian mitochondrial transcription factor A (TFAM) is encoded in the nucleus and imported into mitochondria, where it functions as an activator of mtDNA transcription and packages mtDNA into DNA-protein aggregates called mitochondrial nucleoids. Two X-ray crystallography studies in this issue reveal that TFAM shapes mtDNA into a sharp U-turn, thereby providing a molecular mechanism for its dual roles in the expression and maintenance of mtDNA.
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| 2. |
- Larsson, Anton J M, et al.
(författare)
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X-chromosome upregulation is driven by increased burst frequency
- 2019
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Ingår i: Nature Structural & Molecular Biology. - Stockholm : Karolinska Institutet, Dept of Medical Biochemistry and Biophysics. - 1545-9993 .- 1545-9985.
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Tidskriftsartikel (refereegranskat)abstract
- Ohno's hypothesis postulates that X-chromosome upregulation rectifies X-dose imbalance relative to autosomal genes, present in two active copies per cell. Here we dissected X-upregulation into kinetics of transcription, inferred from allele-specific single-cell RNA-sequencing (scRNAseq) data from somatic mouse cells. We confirmed increased X-chromosome expression in female and male somatic cells, and remarkably found that the X-chromosome achieved upregulation by elevated burst frequencies. By monitoring differentiating female embryonic stem cells, we found that elevated burst frequency established on the active X-chromosome as X-inactivation occurred on the other allele. This provides mechanistic insights into X-chromosome upregulation.
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| 3. |
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| 4. |
- Akke, Mikael
(författare)
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Out of hot water
- 2004
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9985 .- 1545-9993. ; 11:10, s. 912-913
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Tidskriftsartikel (refereegranskat)abstract
- A recent study of adenylate kinase reveals that conformational dynamics in control product release and determine the rate-limiting step in the overall catalytic reaction.
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| 5. |
- Ameur, Adam, et al.
(författare)
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Total RNA sequencing reveals nascent transcription and widespread co-transcriptional splicing in the human brain
- 2011
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 18:12, s. 1435-1440
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptome sequencing allows for analysis of mature RNAs at base pair resolution. Here we show that RNA-seq can also be used for studying nascent RNAs undergoing transcription. We sequenced total RNA from human brain and liver and found a large fraction of reads (up to 40%) within introns. Intronic RNAs were abundant in brain tissue, particularly for genes involved in axonal growth and synaptic transmission. Moreover, we detected significant differences in intronic RNA levels between fetal and adult brains. We show that the pattern of intronic sequence read coverage is explained by nascent transcription in combination with co-transcriptional splicing. Further analysis of co-transcriptional splicing indicates a correlation between slowly removed introns and alternative splicing. Our data show that sequencing of total RNA provides unique insight into the transcriptional processes in the cell, with particular importance for normal brain development.
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| 6. |
- Anandapadmanaban, Madhanagopal, et al.
(författare)
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High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation
- 2013
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Ingår i: Nature Structural & Molecular Biology. - : NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA. - 1545-9993 .- 1545-9985. ; 20:8, s. 1008-
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Tidskriftsartikel (refereegranskat)abstract
- The general transcription factor TFIID provides a regulatory platform for transcription initiation. Here we present the crystal structure (1.97 angstrom) and NMR analysis of yeast TAF1 N-terminal domains TAND1 and TAND2 bound to yeast TBP, together with mutational data. We find that yeast TAF1-TAND1, which in itself acts as a transcriptional activator, binds TBPs concave DNA-binding surface by presenting similar anchor residues to TBP as does Mot1 but from a distinct structural scaffold. Furthermore, we show how TAF1-TAND2 uses an aromatic and acidic anchoring pattern to bind a conserved TBP surface groove traversing the basic helix region, and we find highly similar TBP-binding motifs also presented by the structurally distinct TFIIA, Mot1 and Brf1 proteins. Our identification of these anchoring patterns, which can be easily disrupted or enhanced, provides insight into the competitive multiprotein TBP interplay critical to transcriptional regulation.
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| 7. |
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| 8. |
- Asami, Jinta, et al.
(författare)
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Structural basis of hepatitis B virus receptor binding
- 2024
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Ingår i: Nature Structural & Molecular Biology. - 1545-9993 .- 1545-9985. ; 31, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV), a leading cause of developing hepatocellular carcinoma affecting more than 290 million people worldwide, is an enveloped DNA virus specifically infecting hepatocytes. Myristoylated preS1 domain of the HBV large surface protein binds to the host receptor sodium-taurocholate cotransporting polypeptide (NTCP), a hepatocellular bile acid transporter, to initiate viral entry. Here, we report the cryogenic-electron microscopy structure of the myristoylated preS1 (residues 2–48) peptide bound to human NTCP. The unexpectedly folded N-terminal half of the peptide embeds deeply into the outward-facing tunnel of NTCP, whereas the C-terminal half formed extensive contacts on the extracellular surface. Our findings reveal an unprecedented induced-fit mechanism for establishing high-affinity virus–host attachment and provide a blueprint for the rational design of anti-HBV drugs targeting virus entry.
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| 9. |
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| 10. |
- Banci, L, et al.
(författare)
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Structural proteomics: from the molecule to the system
- 2007
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Ingår i: Nature structural & molecular biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 14:1, s. 3-4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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