| 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. |
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| 3. |
- 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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| 4. |
- 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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| 5. |
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| 6. |
- Doerig, Christian, et al.
(författare)
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A parasite calcium switch and Achilles' heel revealed
- 2010
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 17:5, s. 541-543
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Egelhofer, Thea A, et al.
(författare)
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An assessment of histone-modification antibody quality
- 2011
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 18:1, s. 91-93
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Tidskriftsartikel (refereegranskat)abstract
- We have tested the specificity and utility of more than 200 antibodies raised against 57 different histone modifications in Drosophila melanogaster, Caenorhabditis elegans and human cells. Although most antibodies performed well, more than 25% failed specificity tests by dot blot or western blot. Among specific antibodies, more than 20% failed in chromatin immunoprecipitation experiments. We advise rigorous testing of histone-modification antibodies before use, and we provide a website for posting new test results (http://compbio.med.harvard.edu/antibodies/).
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| 8. |
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| 9. |
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| 10. |
- Gianni, Stefano, et al.
(författare)
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Structural characterization of a misfolded intermediate populated during the folding process of a PDZ domain
- 2010
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 17:12, s. 1431-1437
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Tidskriftsartikel (refereegranskat)abstract
- Incorrectly folded states transiently populated during the protein folding process are potentially prone to aggregation and have been implicated in a range of misfolding disorders that include Alzheimer's and Parkinson's diseases. Despite their importance, however, the structures of these states and the mechanism of their formation have largely escaped detailed characterization because of their short-lived nature. Here we present the structures of all the major states involved in the folding process of a PDZ domain, which include an off-pathway misfolded intermediate. By using a combination of kinetic, protein engineering, biophysical and computational techniques, we show that the misfolded intermediate is characterized by an alternative packing of the N-terminal β-hairpin onto an otherwise native-like scaffold. Our results suggest a mechanism of formation of incorrectly folded transient compact states by which misfolded structural elements are assembled together with more extended native-like regions.
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