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  • Barends, Thomas R. M., et al. (författare)
  • Structure and mechanism of a bacterial light-regulated cyclic nucleotide phosphodiesterase
  • 2009
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 459, s. 1015-1018
  • Tidskriftsartikel (refereegranskat)abstract
    • The ability to respond to light is crucial for most organisms. BLUF is a recently identified photoreceptor protein domain that senses blue light using a FAD chromophore. BLUF domains are present in various proteins from the Bacteria, Euglenozoa and Fungi. Although structures of single-domain BLUF proteins have been determined, none are available for a BLUF protein containing a functional output domain; the mechanism of light activation in this new class of photoreceptors has thus remained poorly understood. Here we report the biochemical, structural and mechanistic characterization of a full-length, active photoreceptor, BlrP1 (also known as KPN_01598), from Klebsiella pneumoniae. BlrP1 consists of a BLUF sensor domain and a phosphodiesterase EAL output domain which hydrolyses cyclic dimeric GMP (c-di-GMP). This ubiquitous second messenger controls motility, biofilm formation, virulence and antibiotic resistance in the Bacteria. Crystal structures of BlrP1 complexed with its substrate and metal ions involved in catalysis or in enzyme inhibition provide a detailed understanding of the mechanism of the EAL-domain c-di-GMP phosphodiesterases. These structures also sketch out a path of light activation of the phosphodiesterase output activity. Photon absorption by the BLUF domain of one subunit of the antiparallel BlrP1 homodimer activates the EAL domain of the second subunit through allosteric communication transmitted through conserved domain-domain interfaces.
  • Belonoshko, Anatoly B., et al. (författare)
  • Stability of the body-centred-cubic phase of iron in the Earth's inner core
  • 2003
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 424:6952, s. 1032-1034
  • Tidskriftsartikel (refereegranskat)abstract
    • Iron is thought to be the main constituent of the Earth's core(1), and considerable efforts(2-14) have therefore been made to understand its properties at high pressure and temperature. While these efforts have expanded our knowledge of the iron phase diagram, there remain some significant inconsistencies, the most notable being the difference between the 'low' and 'high' melting curves(15). Here we report the results of molecular dynamics simulations of iron based on embedded atom models fitted to the results of two implementations of density functional theory. We tested two model approximations and found that both point to the stability of the body-centred-cubic (b.c.c.) iron phase at high temperature and pressure. Our calculated melting curve is in agreement with the 'high' melting curve, but our calculated phase boundary between the hexagonal close packed (h. c. p.) and b.c.c. iron phases is in good agreement with the 'low' melting curve. We suggest that the h.c.p.-b.c.c. transition was previously misinterpreted as a melting transition, similar to the case of xenon(16-18), and that the b.c.c. phase of iron is the stable phase in the Earth's inner core.
  • Berggren, Gustav, et al. (författare)
  • Biomimetic assembly and activation of [FeFe]-hydrogenases
  • 2013
  • Ingår i: Nature. - Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.. - 0028-0836 .- 1476-4687. ; 499:7456, s. 66-69
  • Tidskriftsartikel (refereegranskat)
  • Besnier, Francois, et al. (författare)
  • Whole-genome resequencing reveals loci under selection during chicken domestication
  • 2010
  • Ingår i: Nature. - Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 464, s. 587-U145
  • Tidskriftsartikel (refereegranskat)abstract
    • Domestic animals are excellent models for genetic studies of phenotypic evolution(1-3). They have evolved genetic adaptations to a new environment, the farm, and have been subjected to strong human-driven selection leading to remarkable phenotypic changes in morphology, physiology and behaviour. Identifying the genetic changes underlying these developments provides new insight into general mechanisms by which genetic variation shapes phenotypic diversity. Here we describe the use of massively parallel sequencing to identify selective sweeps of favourable alleles and candidate mutations that have had a prominent role in the domestication of chickens (Gallus gallus domesticus) and their subsequent specialization into broiler (meat-producing) and layer (egg-producing) chickens. We have generated 44.5-fold coverage of the chicken genome using pools of genomic DNA representing eight different populations of domestic chickens as well as red jungle fowl (Gallus gallus), the major wild ancestor(4). We report more than 7,000,000 single nucleotide polymorphisms, almost 1,300 deletions and a number of putative selective sweeps. One of the most striking selective sweeps found in all domestic chickens occurred at the locus for thyroid stimulating hormone receptor (TSHR), which has a pivotal role in metabolic regulation and photoperiod control of reproduction in vertebrates. Several of the selective sweeps detected in broilers overlapped genes associated with growth, appetite and metabolic regulation. We found little evidence that selection for loss-of-function mutations had a prominent role in chicken domestication, but we detected two deletions in coding sequences that we suggest are functionally important. This study has direct application to animal breeding and enhances the importance of the domestic chicken as a model organism for biomedical research.
  • Beznosov, Pavel A., et al. (författare)
  • Morphology of the earliest reconstructable tetrapod Parmastega aelidae
  • 2019
  • Ingår i: Nature. - NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 574:7779, s. 527-531
  • Tidskriftsartikel (refereegranskat)abstract
    • The known diversity of tetrapods of the Devonian period has increased markedly in recent decades, but their fossil record consists mostly of tantalizing fragments(1-15). The framework for interpreting the morphology and palaeobiology of Devonian tetrapods is dominated by the near complete fossils of Ichthyostega and Acanthostega; the less complete, but partly reconstructable, Ventastega and Tulerpeton have supporting roles(2,4,16-34). All four of these genera date to the late Famennian age (about 365-359 million years ago)-they are 10 million years younger than the earliest known tetrapod fragments(5,10), and nearly 30 million years younger than the oldest known tetrapod footprints(35). Here we describe Parmastega aelidae gen. et sp. nov., a tetrapod from Russia dated to the earliest Famennian age (about 372 million years ago), represented by three-dimensional material that enables the reconstruction of the skull and shoulder girdle. The raised orbits, lateral line canals and weakly ossified postcranial skeleton of P. aelidae suggest a largely aquatic, surface-cruising animal. In Bayesian and parsimony-based phylogenetic analyses, the majority of trees place Parmastega as a sister group to all other tetrapods.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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