| 1. |
- Dods, Robert, 1989, et al.
(författare)
-
From Macrocrystals to Microcrystals: A Strategy for Membrane Protein Serial Crystallography.
- 2017
-
Ingår i: Structure. - : Elsevier BV. - 1878-4186 .- 0969-2126. ; 25:9, s. 1461-1468
-
Tidskriftsartikel (refereegranskat)abstract
- Serial protein crystallography was developed at X-ray free-electron lasers (XFELs) and is now also being applied at storage ring facilities. Robust strategies for the growth and optimization of microcrystals are needed to advance the field. Here we illustrate a generic strategy for recovering high-density homogeneous samples of microcrystals starting from conditions known to yield large (macro) crystals of the photosynthetic reaction center of Blastochloris viridis (RCvir). We first crushed these crystals prior to multiple rounds of microseeding. Each cycle of microseeding facilitated improvements in the RCvir serial femtosecond crystallography (SFX) structure from 3.3-Å to 2.4-Å resolution. This approach may allow known crystallization conditions for other proteins to be adapted to exploit novel scientific opportunities created by serial crystallography.
|
|
| 2. |
- Dods, Robert, 1989, et al.
(författare)
-
Ultrafast structural changes within a photosynthetic reaction centre.
- 2021
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7841, s. 310-314
-
Tidskriftsartikel (refereegranskat)abstract
- Photosynthetic reaction centres harvest the energy content of sunlight by transporting electrons across an energy-transducing biological membrane. Here we use time-resolved serial femtosecond crystallography1 using an X-ray free-electron laser2 to observe light-induced structural changes in the photosynthetic reaction centre of Blastochloris viridis on a timescale of picoseconds. Structural perturbations first occur at the special pair of chlorophyll molecules of the photosynthetic reaction centre that are photo-oxidized by light. Electron transfer to the menaquinone acceptor on the opposite side of the membrane induces a movement of this cofactor together with lower amplitude protein rearrangements. These observations reveal how proteins use conformational dynamics to stabilize the charge-separation steps of electron-transfer reactions.
|
|
| 3. |
- Temperton, Robert H., et al.
(författare)
-
Resonant X-ray photo-oxidation of light-harvesting iron (II/III) N-heterocyclic carbene complexes
- 2021
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Two photoactive iron N-heterocyclic carbene complexes [FeII(btz)2(bpy)]2+ and [FeIII(btz)3]3+, where btz is 3,3’-dimethyl-1,1’-bis(p-tolyl)-4,4’-bis(1,2,3-triazol-5-ylidene) and bpy is 2,2’-bipyridine, have been investigated by Resonant Photoelectron Spectroscopy (RPES). Tuning the incident X-ray photon energy to match core-valence excitations provides a site specific probe of the electronic structure properties and ligand-field interactions, as well as information about the resonantly photo-oxidised final states. Comparing measurements of the Fe centre and the surrounding ligands demonstrate strong mixing of the Fe t 2 g levels with occupied ligand π orbitals but weak mixing with the corresponding unoccupied ligand orbitals. This highlights the importance of π-accepting and -donating considerations in ligand design strategies for photofunctional iron carbene complexes. Spin-propensity is also observed as a final-state effect in the RPES measurements of the open-shell Fe III complex. Vibronic coupling is evident in both complexes, where the energy dispersion hints at a vibrationally hot final state. The results demonstrate the significant impact of the iron oxidation state on the frontier electronic structure and highlights the differences between the emerging class of Fe III photosensitizers from those of more traditional Fe II complexes.
|
|
| 4. |
- Temperton, Robert H., et al.
(författare)
-
Site-Selective Orbital Interactions in an Ultrathin Iron-Carbene Photosensitizer Film
- 2020
-
Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 124:8, s. 1603-1609
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first experimental study of the frontier orbitals in an ultrathin film of the novel hexa-carbene photosensitizer [Fe(btz)3]3+, where btz is 3,3′-dimethyl-1,1′-bis(p-tolyl)-4,4′-bis(1,2,3-triazol-5-ylidene). Resonant photoelectron spectroscopy (RPES) was used to probe the electronic structure of films where the molecular and oxidative integrities had been confirmed with optical and X-ray spectroscopies. In combination with density functional theory calculations, RPES measurements provided direct and site-selective information about localization and interactions of occupied and unoccupied molecular orbitals. Fe 2p, N 1s, and C 1s measurements selectively probed the metal, carbene, and side-group contributions revealing strong metal-ligand orbital mixing of the frontier orbitals. This helps explain the remarkable photophysical properties of iron-carbenes in terms of unconventional electronic structure properties and favorable metal-ligand bonding interactions - important for the continued development of these type of complexes toward light-harvesting and light-emitting applications.
|
|
| 5. |
- Collins, Ruairi, et al.
(författare)
-
Biochemical discrimination between selenium and sulfur 1 : a single residue provides selenium specificity to human selenocysteine lyase
- 2012
-
Ingår i: PLoS One. - Stockholm : Karolinska Institutet, Dept of Medical Biochemistry and Biophysics. - 1932-6203.
-
Tidskriftsartikel (refereegranskat)abstract
- Selenium and sulfur are two closely related basic elements utilized in nature for a vast array of biochemical reactions. While toxic at higher concentrations, selenium is an essential trace element incorporated into selenoproteins as selenocysteine (Sec), the selenium analogue of cysteine (Cys). Sec lyases (SCLs) and Cys desulfurases (CDs) catalyze the removal of selenium or sulfur from Sec or Cys and generally act on both substrates. In contrast, human SCL (hSCL) is specific for Sec although the only difference between Sec and Cys is the identity of a single atom. The chemical basis of this selenium-over-sulfur discrimination is not understood. Here we describe the X-ray crystal structure of hSCL and identify Asp146 as the key residue that provides the Sec specificity. A D146K variant resulted in loss of Sec specificity and appearance of CD activity. A dynamic active site segment also provides the structural prerequisites for direct product delivery of selenide produced by Sec cleavage, thus avoiding release of reactive selenide species into the cell. We thus here define a molecular determinant for enzymatic specificity discrimination between a single selenium versus sulfur atom, elements with very similar chemical properties. Our findings thus provide molecular insights into a key level of control in human selenium and selenoprotein turnover and metabolism.
|
|
| 6. |
- Schmidt, Kenneth A., et al.
(författare)
-
Consequences of information use in breeding habitat selection on the evolution of settlement time
- 2015
-
Ingår i: Oikos. - : Wiley. - 1600-0706 .- 0030-1299. ; 124:1, s. 69-80
-
Tidskriftsartikel (refereegranskat)abstract
- The role of temporal changes and spatial variability in predation risk and prey's means of mitigating such risks is poorly understood in the context of potential threats of global climate change for migratory birds. Yet nest predation, for example, represents a primary source of reproductive mortality in birds. To assess risk birds must spend time prospecting potential breeding sites for cues or signals of predator presence. However, competition for breeding sites with advantage to prior residency poses an evolutionary dilemma as individuals also benefit from early settling. We develop a model to examine adaptive prospecting time for predator cues on breeding grounds characterized by spatial heterogeneity in nest predation risk. We study how populations respond to environmental change represented by variation in habitat specific levels of nest predation, habitat composition, population vital rates, and availability of information (via prospecting) in the form of acoustic predator cues. We identify two mechanisms that regulate and buffer impacts of environmental change on populations. First, the adaptive response to lower population abundance under deteriorating environmental conditions is to increase prospecting time, which in turn increases individuals nest success to counteract population declines. This occurs because reduced competition for sites decreases the benefit of early settlement. Second, per capita success in site choice increases during population declines owing to reduced competition that increases the availability of good sites. We also show that the increased benefit to settling early when competition increases can lead to the paradoxical result that with greater spatial heterogeneity, less effort is placed on discerning good and bad sites. Our analysis thus contributes several novel results by which nest predation, settlement phenology, prospecting time and information gathering can influence species capacity to adapt to changing environments.
|
|
| 7. |
- Weinstein, John N., et al.
(författare)
-
The cancer genome atlas pan-cancer analysis project
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
-
Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
|
|
| 8. |
- Dewhurst, Richard, et al.
(författare)
-
How task demands influence scanpath similarity in a sequential number-search task
- 2018
-
Ingår i: Vision Research. - : Elsevier BV. - 1878-5646 .- 0042-6989. ; , s. 9-23
-
Tidskriftsartikel (refereegranskat)abstract
- More and more researchers are considering the omnibus eye movement sequence—the scanpath—in their studies of visual and cognitive processing (e.g. Hayes, Petrov, & Sederberg, 2011; Madsen, Larson, Loschky, & Rebello, 2012; Ni et al., 2011; von der Malsburg & Vasishth, 2011). However, it remains unclear how recent methods for comparing scanpaths perform in experiments producing variable scanpaths, and whether these methods supplement more traditional analyses of individual oculomotor statistics. We address this problem for MultiMatch (Jarodzka et al., 2010; Dewhurst et al., 2012), evaluating its performance with a visual search-like task in which participants must fixate a series of target numbers in a prescribed order. This task should produce predictable sequences of fixations and thus provide a testing ground for scanpath measures. Task difficulty was manipulated by making the targets more or less visible through changes in font and the presence of distractors or visual noise. These changes in task demands led to slower search and more fixations. Importantly, they also resulted in a reduction in the between-subjects scanpath similarity, demonstrating that participants’ gaze patterns became more heterogenous in terms of saccade length and angle, and fixation position. This implies a divergent strategy or random component to eye-movement behaviour which increases as the task becomes more difficult. Interestingly, the duration of fixations along aligned vectors showed the opposite pattern, becoming more similar between observers in 2 of the 3 difficulty manipulations. This provides important information for vision scientists who may wish to use scanpath metrics to quantify variations in gaze across a spectrum of perceptual and cognitive tasks. © 2018 Elsevier Ltd
|
|
| 9. |
- Evangelou, Evangelos, et al.
(författare)
-
Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
-
Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
|
|
| 10. |
- Huang, TS, et al.
(författare)
-
A cell adhesion protein from the crayfish Pacifastacus leniusculus, a serine proteinase homologue similar to Drosophila masquerade
- 2000
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 275:14, s. 9996-10001
-
Tidskriftsartikel (refereegranskat)abstract
- A cDNA encoding a protein resembling masquerade, a serine proteinase homologue expressed during embryogenesis, larval, and pupal development in Drosophila melanogaster, was identified in hemocytes of the adult freshwater crayfish, Pacifastacus leniusculus. The crayfish protein is similar to Drosophila masquerade in the following aspects: (a) overall sequence of the serine proteinase domain, such as the position of three putative disulfide bridges, glycine in the place of the catalytic serine residue, and the presence of a substrate-lining pocket typical for trypsins; (b) the presence of several copies of a disulfide-knotted motif in the putative propeptide. This masquerade-like protein is cleaved into a 27-kDa fragment, which could be detected by immunoblot analysis using an affinity-purified antibody against a synthetic peptide in the C-terminal domain of the protein. The 27-kDa protein could be immunoaffinity-purified from hemocyte lysate supernatant and exhibited cell adhesion activity in vitro, indicating that the C-terminal domain of the crayfish masquerade-like protein mediates cell adhesion.
|
|
