The interaction of fluorinated glycomimetics with DC-SIGN: multiple binding modes disentangled by the combination of NMR methods and MD simulations

Fluorinated glycomimetics are frequently employed to study and eventually modulate protein–glycan interactions. However, complex glycans and their glycomimetics may display multiple binding epitopes that enormously complicate the access to a complete picture of the protein–ligand complexes. We herein present a new methodology based on the synergic combination of experimental 19F-based saturation transfer difference (STD) NMR data with computational protocols, applied to analyze the interaction between DC-SIGN, a key lectin involved in inflammation and infection events with the trifluorinated glycomimetic of the trimannoside core, ubiquitous in human glycoproteins. A novel 2D-STD-TOCSYreF NMR experiment was employed to obtain the experimental STD NMR intensities, while the Complete Relaxation Matrix Analysis (CORCEMA-ST) was used to predict that expected for an ensemble of geometries extracted from extensive MD simulations. Then, an in-house built computer program was devised to find the ensemble of structures that provide the best fit between the theoretical and the observed STD data. Remarkably, the experimental STD profiles obtained for the ligand/DC-SIGN complex could not be satisfactorily explained by a single binding mode, but rather with a combination of different modes coexisting in solution. Therefore, the method provides a precise view of those ligand–receptor complexes present in solution.We thank Agencia Estatal de Investigación (Spain) for grants RTI2018-094751-B-C21 and B-C22, CTQ2015-68756-R, and for FPI and FPU fellowships to J.D.M. and P.V., respectively, and for the Severo Ochoa Excellence Accreditation (SEV-2016-0644). J.J.-B. also thanks to the European Research Council (RECGLYCANMR, Advanced Grant no. 788143). S.O. thanks the SFI Award 13/IA/1959Peer reviewe

Minimizing the entropy penalty for ligand binding: lessons from the molecular recognition of the histo blood-group antigens by human galectin-3

6 p.-5 fig.-2 tab.Ligand conformational entropy plays an important role in carbohydrate recognition events. Glycans are characterized by intrinsic flexibility around the glycosidic linkages, thus in most cases, loss of conformational entropy of the sugar upon complex formation strongly affects the entropy of the binding process. By employing a multidisciplinary approach combining structural, conformational, binding energy, and kinetic information, we investigated the role of conformational entropy in the recognition of the histo blood‐group antigens A and B by human galectin‐3, a lectin of biomedical interest. We show that these rigid natural antigens are pre‐organized ligands for hGal‐3, and that restriction of the conformational flexibility by the branched fucose (Fuc) residue modulates the thermodynamics and kinetics of the binding process. These results highlight the importance of glycan flexibility and provide inspiration for the design of high‐affinity ligands as antagonists for lectins.We thank Agencia Estatal de Investigacion and ISCIII of Spain and the European Research Council for financial support.Peer reviewe

Mapa Geológico de España E 1:200000, hoja 69, Pozoblanco

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Plutonismo Pérmico-Carbonífero alumino-potásico en la Zona Surportuguesa. El granito cordierítico de El Crispinejo

En el Batolito de la Sierra Norte hay un evento plutónico tardío, poco conocido, caracterizado por pequeños plutones graníticos peralumínicos, ricos en cordierita, siendo el plutón de El Crispinejo el que presenta las mejores relaciones de campo para realizar este tipo de estudio. Este plutón intruye en materiales del Devónico, el Complejo Vulcano-Sedimentario y las rocas ígneas del Batolito de la Sierra Norte. Estos plutones muestra una buena respuesta geofísica-radiométrica (K-Th-U), en especial por su alto contenido en K, en contraste con los granitoides trondhjemíticos que forman parte de la serie TTG del BSN. Una edad U-Pb ID-TIMS concordante de 300.5 ± 0.5 Ma obtenida en monacitas apunta a la existencia de un evento magmático tardi-Varisco en la Zona Surportuguesa, que se sitúa en el tránsito entre Carbonífero-Pérmico. Esta actividad ígnea podría estar relacionada con una serie de indicios mineros (F-Pb-Zn, Sn-W) completamente distintos a los que caracterizan a la Faja Pirítica Ibérica (sulfuros masivos y manganeso).Unidad de Salamanca, Instituto Geológico y Minero de España, EspañaUnidad de Tres Cantos, Instituto Geológico y Minero de España, EspañaInstituto Geológico y Minero de España, Españ

Quaternary deformation and uplift of coral reef terraces produced by oblique subduction and underthrusting of the Bahama Platform below the northern Hispaniola forearc

[EN] Active tectonics linked to the rise of the Hispaniola forearc explain the morphological characteristics, spatial distribution and U-Th geochronological ages of the uplifted coral reef terraces of the La Isabela Formation in both the eastern Cordillera Septentrional and the Saman ́a Peninsula of northeastern Dominican Republic. Depositional coral reef terraces of MIS 5e (TII), 7e (TIII) and 9 (TIV) stages occur respectively at maximum heights of about 25 m, 80 m and 120 m above the current sea level. The development of heterogeneous brittle deformation structures in the coral limestone at all scales document active tectonics and include small faults, shear fractures, extensional joints and calcite veins. Their geometric and kinematic characteristics, as well as the stress tensors calculated from fault-slip and fracture orientation data, are all compatible with ENE to NE-trending regional shortening, and indicate that a left-lateral transpressive regime is deforming the forearc during the Quaternary. Along the northern Hispaniola coastline, the tectonic uplift mimics the distribution of the bathymetric features on the subducting Bahamas Platform, outboard the Hispaniola-Puerto Rico Trench. The highest calculated uplift rates in the eastern Cordillera Septentrional and Saman ́a Peninsula correspond to the collision zone of the Silver Spur and Navidad Bank (≥0.4 m/ka), respectively. Uplift rates decrease towards the west (≤0.2 m/ka), where the oblique collision of carbonate ridges and related forearc deformation would not have been recorded since at least the Early Pleistocene. Oblique subduction and underthrusting of the Bahamas Platform followed by basal erosion at the subduction channel explain the observed time-transgressive pattern of uplift and subsidence in the northern Hispaniola forearc and the change from accretionary to erosive processes in the convergent margin.The research has been funded by Spanish CGL2012-33669/BTE project, as well as through the PRX12/00152 grant to the first author. The second author acknowledge a postdoctoral grant of the Basque Country Government.Peer reviewe

U-Pb dating of Ordovician felsic volcanism in the Schistose Domain of the Galicia-Trás-os-Montes Zone near Cabo Ortegal (NW Spain)

The northern termination of the Schistose Domain of the Galicia-Trás-os-Montes Zone is a tectonic slice named the Rio Baio Thrust Sheet, which is sandwiched between the Cabo Ortegal Complex and the Ollo de Sapo Domain of the Central-Iberian Zone. The Rio Baio Thrust Sheet is formed by two volcanosedimentary series, the Loiba and the Queiroga Series. The Loiba Series contains calc-alkaline dacite and rhyolite, while the overlying Queiroga Series has alkaline rhyolite. These series were considered to be in stratigraphically upwards continuity and believed to be Silurian in age. U-Pb dating of an alkaline rhyolite in the Queiroga Series provides an Arenig age of 475 ± 2 Ma. This age makes the Queiroga Series the oldest known stratigraphic unit in the Schistose Domain of the Galicia-Trás-os-Montes Zone, impeding correlation between the lithostratigraphic sequences of Ortegal and Central Galicia. As well as providing evidence of an unforeseen structural complexity within the Rio Baio Sheet, the new data supports the notion that the Schistose Domain is not parautochtonous, but a separate lithotectonic unit in thrust contact with the underlying Central-Iberian Zone

From intra-oceanic subduction to arc accretion and arc-continent collision: insights from the structural evolution of the Río San Juan metamorphic complex, northern Hispaniola

The Río San Juan metamorphic complex exposes a segment of a high-pressure subduction-accretionary complex built during Caribbean island arc-North America continental margin convergence. It is composed of accreted arc- and oceanic-derived metaigneous rocks, serpentinized peridotites and minor metasediments forming a structural pile. Combined detailed mapping, structural and metamorphic analysis, and geochronology show that the deformation can be divided into five main events (D1eD5). An early subduction-related D1 deformation and M1 metamorphism produced greenschist (mafic rocks of the Gaspar Hernández peridotite-tectonite), blueschist and eclogite (metamafic blocks in the Jagua Clara mélange), high-P epidote-amphibolite and eclogite (Cuaba unit), and lower blueschist and greenschist-facies conditions (Morrito unit). This was followed by M2 decompression and cooling in the blueschist, greenschist and low-P amphibolite-facies conditions. The shape of the retrograde P-T path, the age of the exhumation-related D2 structures, and the tectonic significance of D2 deformation are different in each structural unit. Published UePb and 40Ar/39Ar plateau ages and T-t/P-t estimations reveal diachronic Turonian-Coniacian to Maastrichtian retrograde M2 metamorphism in the different structural units of the complex, during a consistent D2 top-to-the-NE/ENE tectonic transport. Regionally, a similar top-to-the-ENE tectonic transport also took place in the metasedimentary nappes of the Samaná complex during the Eocene to earliest Miocene. This kinematic compatibility indicates a general northeastward progradation of deformation in the northern Caribbean convergent margin, as the successive tectonic incorporation of arc, oceanic and continental-derived terrains to the developing Caribbean subduction-accretionary complex took place. D3eD5 deformations are discontinuous and much less penetrative, recording the evolution from ductile to brittle conditions of deformation in the complex. The D3 event substantially modified the nappe-stack and produced open folds with amplitudes up to kilometer-scale. The Late Paleocene-Eocene D4 structures are ductile to ductile-brittle thrusts and inverse shear bands. D5 is a Tertiary, entirely brittle deformation that had considerable influence in the geometry of the whole complex. From the Miocene to the Present, it has been cut and laterally displaced by a D5 sinistral strike-slip fault system associated with the Septentrional fault zoneUnidad de Tres Cantos, Instituto Geológico y Minero de España, EspañaInstitut für Geowissenschaften, Universität Mainz, AlemaniaPacific Centre for Isotopic and Geochemical Research, University of British Columbia, CanadáInstitut de Ciències de la Terra Jaume Almera, Españ

Upper Ordovician magmatism in the Central Pyrenees: First U-Pb zircon age from the Pallaresa Massif

Ordovician geodynamics: The Sardic Phase in the Pyrenees, Mouthoumet and Montagne Noire massifs International Meeting (2017. Figueras, España)The Late Ordovician magmatism is well represented in all massifs of the Eastern Pyrenees and the Catalan Coastal Ranges, which contain Upper Ordovician rocks. Nevertheless, data about this magmatic episode in the Central Pyrenees are scarce. This work shows the first geochronological data for Upper Ordovician magmatism in the Pallaresa massif. This massif is a large E-W trend antiformal structure included in the metamorphic structural units of the Pyrenean Axial Zone, where Cambro-Ordovician and Upper Ordovician rocks crop out. The Cambro-Ordovician rocks consist of a low-grade monotonous alternation of quartzites and slates with some limestone and conglomerate intercalations, which show evidence of a pre-Variscan penetrative deformation. The Upper Ordovician succession lies unconformably on the older Cambro-Ordovician beds and is represented by a siliciclastic succession with an intermediate limestone level. Volcanic rock levels have been observed interbedded within what was considered a Cambro-Ordovician succession close to outcrops of Upper Ordovician rocks in the eastern part of Pallaresa massif. Both metasedimentary and volcanic rocks were deformed and metamorphosed during the Variscan Orogeny.The volcanic rocks are rhyodacitic to dacitic crystal-rich meta-tuffs with a pervasive foliation. Their mineralogical composition is mainly volcanic quartz, feldspar and biotite. The matrix consists of fine grained of biotite, muscovite, quartz and clinozoisite, the latter mainly developed in highly deformed bands. In addition to these mineral phases, idiomorphic crystals of zircon are recognized.Instituto Geológico y Minero de España, EspañaDepartamento de Geología, Universidad de Oviedo, EspañaPeer reviewe

Geochemistry and Lithosphere Geodynamics group (Geoquímica y Geodinámica Litosférica, GEOLITHOS)

[EN] The Earth ́s crust has been shaped as result of the chemical differentiation processes behind the phenomena of magmatism and formation of igneous rocks, and the transformation of rocks by metamorphism. Magmatism and metamorphism are key to understand how the lithosphere dynamics and Earth’s plate tectonics system work. New oceanic crust is formed by melting of the mantle at spreading ocean ridges. As this newly formed crust ages and gets transformed by metamorphism, it becomes denser, collapsing and sinking into the mantle forming a subduction zone. New continental crust is formed in the volcanic arcs above subduction zones by flux melting of the down-going plateand the overlying mantle, generating new magmas that form a felsic, buoyant, and thicker continental crust. Subduction zones are destructive plate margins where oceans are been consumed leading to the collision of continental crust and the formation of orogenic belts. As a group, we are interested in these igneous and metamorphic processes and their fundamental role in shaping the dynamics of Earth ́s lithosphere. We have an extensive experience mapping metamorphic and igneous complexes in the Iberian Massif and overseas (e.g. Caribbean orogen, Angolan craton); and bridging fieldwork with detailed petrological and geochemical studies and instrumental analytical work. Our group is formed by scientist that belonged to the former Geology and Geophysics and the Analytical Laboratories units of IGME. Our common interest is the use of petrological tools and analytical instrumentation to decipher the geological evolution and architecture of the Earth ́s crust studying the texture, mineral and chemical composition ofigneous and metamorphic rocks.Peer reviewe

Timing of deformational events in the Río San Juan complex: implications for the tectonic controls on the exhumation of high-P rocks in the northern Caribbean subduction-accretionary prism

An integrated structural, petrological and geochronological study was undertaken to constrain the tectonic history and controls on the exhumation of the high-P rocks of the Río San Juan complex in the northern Caribbean subduction–accretionary wedge. In the main structural units of the complex, microtextural analyses were performed to identify the fabrics formed at peak ofmetamorphismin eclogite-facies conditions and during the main retrogressive event toward the low-P amphibolite or blueschist/greenschist-facies conditions. U–Pb SHRIMP dating on zircon rims (71.3 ± 0.7 Ma) coupled with 40Ar–39Ar analyses on phengite (~70– 69 Ma) in felsic sills placed temporal constraints on the exhumation of the Jagua Clara serpentinite-matrix mélange during the blueschist-facies stage at the early Maastrichtian. In the Cuaba unit, U–Pb TIMS zircon ages of 89.7 ± 0.1 Ma and 90.1 ± 0.2 Ma obtained for the crystallization of tonalitic/trondhjemitic melts in the lower Guaconejo and upper Jobito subunits, respectively, are similar. These ages coupled with a U–Pb SHRIMP zircon age of 87 ± 1.8 Ma obtained in a garnet amphibolite and a group of older 40Ar–39Ar cooling ages on calcic amphibole constrain the exhumation of the Guaconejo subunit from the high-P stage to the low-P stage at the ~90–83 Ma time interval. Further, the age data collectively supports a genetic relationship between the distributed extensional ductile shearing, the related decompression and the local partial anatexis in the subunit, at least from the Turonian–Coniacian boundary to the early Campanian. A group of younger 40Ar–39Ar ages obtained in themylonitized amphibolites of the basal Jobito detachment zone indicates late ductile deformation and exhumation/cooling in the late Campanian to Maastrichtian (~75–70 Ma). Therefore, structural and age data established deformation partitioning and reworking of retrograde fabrics during ~20 Ma in the Cuaba unit. The different exhumation rates obtained for the Jagua Clara mélange can be explained by uplift in two contrasting tectonic settings: a first stage of slow exhumation (1.4 mm/yr) in the subduction channel, largely lower than plate velocities, and a second stage of relatively fast exhumation (7.6 mm/yr) up to the surface. Therefore, the exhumation was temporally discontinuous and the velocity increase at ~70 Ma probably was triggered in response to the entrance of buoyant material in the subduction zone, such as a Caribeana continental ribbon or the distal part of Yucatán–Bahamas continental margin. In contrast, the exhumation path of the Guaconejo subunit is composed of a first segment from the baric peak to the low-P amphibolite stage (at 84–83 Ma) with an exhumation rate of 7.2 mm/yr, a second segment around the closure temperature of calcic-amphibole (at 82–70 Ma) with a rate of 0.4 mm/yr, and a third segment to the surface exposure (at 60 Ma) with a rate of 1.8 mm/yr. These velocity differences can be correlated with the P–T path proposed for the exhumation of the subunit, with an initial isothermal decompression from the peak in the high-P amphibolite to the eclogite-facies produced by distributed extensional shearing, followed by a relatively slow cooling at low-P in the newly acquired structural position, and the final tectonics mainly partitioned in the late Jobito detachment zone. The initial fast exhumation can be related to a major modification inThis is the IBERSIMS publication number 12. Funding by the Spanish Ministerio Ciencia e Innovación projects CGL2009-08674/BTE and CGL2012-33669/BTE is gratefully acknowledged.Peer Reviewe