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  • 1
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    Revealing conformational substates of lipidated N-Ras protein by pressure modulation [Biophysics and Computational Biology] (2012)
    National Academy of Sciences
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    Publication Date: 2012-01-12
    Description: Regulation of protein function is often linked to a conformational switch triggered by chemical or physical signals. To evaluate such conformational changes and to elucidate the underlying molecular mechanisms of subsequent protein function, experimental identification of conformational substates and characterization of conformational equilibria are mandatory. We apply pressure modulation in combination with FTIR spectroscopy to reveal equilibria between spectroscopically resolved substates of the lipidated signaling protein N-Ras. Pressure has the advantage that its thermodynamic conjugate is volume, a parameter that is directly related to structure. The conformational dynamics of N-Ras in its different nucleotide binding states in the absence and presence of a model biomembrane was probed by pressure perturbation. We show that not only nucleotide binding but also the presence of the membrane has a drastic effect on the conformational dynamics and selection of conformational substates of the protein, and a new substate appearing upon membrane binding could be uncovered. Population of this new substate is accompanied by structural reorientations of the G domain, as also indicated by complementary ATR-FTIR and IRRAS measurements. These findings thus illustrate that the membrane controls signaling conformations by acting as an effective interaction partner, which has consequences for the G-domain orientation of membrane-associated N-Ras, which in turn is known to be critical for its effector and modulator interactions. Finally, these results provide insights into the influence of pressure on Ras-controlled signaling events in organisms living under extreme environmental conditions as they are encountered in the deep sea where pressures reach the kbar range.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 2
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    Structure of human {alpha}TAT1 [Biochemistry] (2012)
    National Academy of Sciences
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    Publication Date: 2012-11-28
    Description: Acetylation of lysine residues is an important posttranslational modification found in all domains of life. α-tubulin is specifically acetylated on lysine 40, a modification that serves to stabilize microtubules of axons and cilia. Whereas histone acetyltransferases have been extensively studied, there is no structural and mechanistic information available on α-tubulin...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    Radar observations of individual rain drops [Earth, Atmospheric, and Planetary Sciences] (2012)
    National Academy of Sciences
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    Publication Date: 2012-06-13
    Description: Atmospheric remote sensing has played a pivotal role in the increasingly sophisticated representation of clouds in the numerical models used to assess global and regional climate change. This has been accomplished because the underlying bulk cloud properties can be derived from a statistical analysis of the returned microwave signals scattered by a diverse ensemble comprised of numerous cloud hydrometeors. A new Doppler radar, previously used to track small debris particles shed from the NASA space shuttle during launch, is shown to also have the capacity to detect individual cloud hydrometeors in the free atmosphere. Similar to the traces left behind on film by subatomic particles, larger cloud particles were observed to leave a well-defined radar signature (or streak), which could be analyzed to infer the underlying particle properties. We examine the unique radar and environmental conditions leading to the formation of the radar streaks and develop a theoretical framework which reveals the regulating role of the background radar reflectivity on their observed characteristics. This main expectation from theory is examined through an analysis of the drop properties inferred from radar and in situ aircraft measurements obtained in two contrasting regions of an observed multicellular storm system. The observations are placed in context of the parent storm circulation through the use of the radar’s unique high-resolution waveforms, which allow the bulk and individual hydrometeor properties to be inferred at the same time.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 4
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    Roco structures explain PD LRRK2 mutations [Biochemistry] (2012)
    National Academy of Sciences
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    Publication Date: 2012-06-27
    Description: Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson disease. Here we show that Dictyostelium discoideum Roco4 is a suitable model to study the structural and biochemical characteristics of the LRRK2 kinase and can be used for optimization of current and identification of new LRRK2 inhibitors. We have solved the structure of Roco4 kinase wild-type, Parkinson disease-related mutants G1179S and L1180T (G2019S and I2020T in LRRK2) and the structure of Roco4 kinase in complex with the LRRK2 inhibitor H1152. Taken together, our data give important insight in the LRRK2 activation mechanism and, most importantly, explain the G2019S-related increase in LRRK2 kinase activity.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    Actions of {phiv}-LITX-Lw1a on ryanodine receptors [Biochemistry] (2013)
    National Academy of Sciences
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    Publication Date: 2013-05-29
    Description: We recently reported the isolation of a scorpion toxin named U1-liotoxin-Lw1a (U1-LITX-Lw1a) that adopts an unusual 3D fold termed the disulfide-directed hairpin (DDH) motif, which is the proposed evolutionary structural precursor of the three-disulfide-containing inhibitor cystine knot (ICK) motif found widely in animals and plants. Here we reveal that U1-LITX-Lw1a...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    Remote Sensing, Vol. 6, Pages 1739-1759: GIS-Based Roughness Derivation for Flood Simulations: A Comparison of Orthophotos, LiDAR and Crowdsourced Geodata (2014)
    MDPI Publishing
    Details
    Publication Date: 2014-02-25
    Description: Natural disasters like floods are a worldwide phenomenon and a serious threat to mankind. Flood simulations are applications of disaster control, which are used for the development of appropriate flood protection. Adequate simulations require not only the geometry but also the roughness of the Earth’s surface, as well as the roughness of the objects hereon. Usually, the floodplain roughness is based on land use/land cover maps derived from orthophotos. This study analyses the applicability of roughness map derivation approaches for flood simulations based on different datasets: orthophotos, LiDAR data, official land use data, OpenStreetMap data and CORINE Land Cover data. Object-based image analysis is applied to orthophotos and LiDAR raster data in order to generate land cover maps, which enable a roughness parameterization. The vertical vegetation structure within the LiDAR point cloud is used to derive an additional floodplain roughness map. Further roughness maps are derived from official land use data, OpenStreetMap and CORINE Land Cover datasets. Six different flood simulations are applied based on one elevation data but with the different roughness maps. The results of the hydrodynamic–numerical models include information on flow velocity and water depth from which the additional attribute flood intensity is calculated of. The results based on roughness maps derived from LiDAR data and OpenStreetMap data are comparable, whereas the results of the other datasets differ significantly.
    Electronic ISSN: 2072-4292
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by MDPI Publishing
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  • 7
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    IJERPH, Vol. 11, Pages 7896-7917: The Historical Distribution of Main Malaria Foci in Spain as Related to Water Bodies (2014)
    MDPI Publishing
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    Publication Date: 2014-08-07
    Description: The possible connectivity between the spatial distribution of water bodies suitable for vectors of malaria and endemic malaria foci in Southern Europe is still not well known. Spain was one of the last countries in Western Europe to be declared free of malaria by the World Health Organization (WHO) in 1964. This study combines, by means of a spatial-temporal analysis, the historical data of patients and deceased with the distribution of water bodies where the disease-transmitting mosquitos proliferate. Therefore, data from historical archives with a Geographic Information System (GIS), using the Inverse Distance Weighted (IDW) interpolation method, was analyzed with the aim of identifying regional differences in the distribution of malaria in Spain. The reasons, why the risk of transmission is concentrated in specific regions, are related to worse socioeconomic conditions (Extremadura), the presence of another vector (Anopheles labranchiae) besides A. atroparvus (Levante) or large areas of water bodies in conditions to reproduce theses vectors (La Mancha and Western Andalusia). In the particular case of Western Andalusia, in 1913, the relatively high percentage of 4.73% of the surface, equal to 202362 ha, corresponds to wetlands and other unhealthy water bodies. These wetlands have been reduced as a result of desiccation policies and climate change such as the Little Ice Age and Global Climate Change. The comprehension of the main factors of these wetland changes in the past can help us interpret accurately the future risk of malaria re-emergence in temperate latitudes, since it reveals the crucial role of unhealthy water bodies on the distribution, endemicity and eradication of malaria in southern Europe.
    Print ISSN: 1661-7827
    Electronic ISSN: 1660-4601
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Published by MDPI Publishing
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