Álvaro Ortega

Bio: Álvaro Ortega is an academic researcher from Spanish National Research Council. The author has contributed to research in topics: Ligand (biochemistry) & Chemotaxis. The author has an hindex of 24, co-authored 55 publications receiving 2306 citations. Previous affiliations of Álvaro Ortega include French Institute of Health and Medical Research & Centre national de la recherche scientifique.

Hydrodynamic properties of rodlike and disklike particles in dilute solution

Abstract: The hydrodynamic properties of cylindrical (rodlike and discoidal) particles in dilute solution have been computed using the bead-shell model treatment. Previous results [Tirado and Garcia de la Torre, J. Chem. Phys. 71, 2581 (1979); 73, 1993 (1980)] for rods with length-to-diameter ratio p>2 are now extended to short cylinders and disks down to p=0.1. The intrinsic viscosity is obtained for rods and disks, and results are presented for the three rotational relaxation times of a cylindrical particle. The hydrodynamic properties are expressed in forms that have a weak variation with p, and are therefore useful for the analysis of experimental values. We present examples of the determination of the length and diameter of the cylindrical particles, for DNA oligonucleotides and tobacco mosaic virus.

Sensory Repertoire of Bacterial Chemoreceptors.

Abstract: Chemoreceptors in bacteria detect a variety of signals and feed this information into chemosensory pathways that represent a major mode of signal transduction. The five chemoreceptors from Escherichia coli have served as traditional models in the study of this protein family. Genome analyses revealed that many bacteria contain much larger numbers of chemoreceptors with broader sensory capabilities. Chemoreceptors differ in topology, sensing mode, cellular location, and, above all, the type of ligand binding domain (LBD). Here, we highlight LBD diversity using well-established and emerging model organisms as well as genomic surveys. Nearly a hundred different types of protein domains that are found in chemoreceptor sequences are known or predicted LBDs, but only a few of them are ubiquitous. LBDs of the same class recognize different ligands, and conversely, the same ligand can be recognized by structurally different LBDs; however, recent studies began to reveal common characteristics in signal-LBD relationships. Although signals can stimulate chemoreceptors in a variety of different ways, diverse LBDs appear to employ a universal transmembrane signaling mechanism. Current and future studies aim to establish relationships between LBD types, the nature of signals that they recognize, and the mechanisms of signal recognition and transduction.

Improved calculation of rotational diffusion and intrinsic viscosity of bead models for macromolecules and nanoparticles.

Abstract: The conventional Kirkwood-Riseman calculation of the hydrodynamic properties of bead models gives abnormal results for rotational quantities and the intrinsic viscosities for models with a few beads or when one bead is dominant. The reason is that beads are treated as point sources of friction. This can be remedied by introducing terms that are neglected in the conventional treatment of orders 0 and -3 in interbead distances. An alternative strategy is the cubic substitution in which each bead is replaced by a cubic array of minibeads. These procedures require a computational overload that, in the case of the intrinsic viscosity, can be avoided using an estimate of the correction due to the nonzero volume of the beads. We have found how such a correction can be estimated from the geometry of the model, and its application yields results that are within the range of typical experimental errors.

FAK dimerization controls its kinase-dependent functions at focal adhesions

Abstract: Focal adhesion kinase (FAK) controls adhesion-dependent cell motility, survival, and proliferation. FAK has kinase-dependent and kinase-independent functions, both of which play major roles in embryogenesis and tumor invasiveness. The precise mechanisms of FAK activation are not known. Using x-ray crystallography, small angle x-ray scattering, and biochemical and functional analyses, we show that the key step for activation of FAK's kinase-dependent functions—autophosphorylation of tyrosine-397—requires site-specific dimerization of FAK. The dimers form via the association of the N-terminal FERM domain of FAK and are stabilized by an interaction between FERM and the C-terminal FAT domain. FAT binds to a basic motif on FERM that regulates co-activation and nuclear localization. FAK dimerization requires local enrichment, which occurs specifically at focal adhesions. Paxillin plays a dual role, by recruiting FAK to focal adhesions and by reinforcing the FAT:FERM interaction. Our results provide a structural and mechanistic framework to explain how FAK combines multiple stimuli into a site-specific function. The dimer interfaces we describe are promising targets for blocking FAK activation.

IgG subclasses and allotypes: from structure to effector functions.

Abstract: Of the five immunoglobulin isotypes, Immunoglobulin G (IgG) is most abundant in human serum. The four subclasses, IgG1, IgG2, IgG3 and IgG4 which are highly conserved, differ in their constant region, particularly in their hinges and upper CH2 domains. These regions are involved in binding to both IgG-Fc receptor (FcγR) and C1q. As a result, the different subclasses have different effector functions, both in terms of triggering FcγR-expressing cells, resulting in phagocytosis or Antibody-dependent cell-mediated cytotoxicity (ADCC), and activating complement. The Fc-regions also contain a binding epitope for the neonatal Fc-receptor (FcRn), responsible for the extended half-life, placental transport, and bidirectional transport of IgG to mucosal surfaces. However, FcRn is also expressed in myeloid cells, where it participates in both phagocytosis and antigen presentation together with classical FcγR and complement. How these properties, IgG-polymorphisms and post-translational modification of the antibodies in the form of glycosylation, affect IgG-function, will be the focus of the current review.

Dynamic root exudate chemistry and microbial substrate preferences drive patterns in rhizosphere microbial community assembly.

Abstract: Like all higher organisms, plants have evolved in the context of a microbial world, shaping both their evolution and their contemporary ecology. Interactions between plant roots and soil microorganisms are critical for plant fitness in natural environments. Given this co-evolution and the pivotal importance of plant-microbial interactions, it has been hypothesized, and a growing body of literature suggests, that plants may regulate the composition of their rhizosphere to promote the growth of microorganisms that improve plant fitness in a given ecosystem. Here, using a combination of comparative genomics and exometabolomics, we show that pre-programmed developmental processes in plants (Avena barbata) result in consistent patterns in the chemical composition of root exudates. This chemical succession in the rhizosphere interacts with microbial metabolite substrate preferences that are predictable from genome sequences. Specifically, we observed a preference by rhizosphere bacteria for consumption of aromatic organic acids exuded by plants (nicotinic, shikimic, salicylic, cinnamic and indole-3-acetic). The combination of these plant exudation traits and microbial substrate uptake traits interact to yield the patterns of microbial community assembly observed in the rhizosphere of an annual grass. This discovery provides a mechanistic underpinning for the process of rhizosphere microbial community assembly and provides an attractive direction for the manipulation of the rhizosphere microbiome for beneficial outcomes.

Dynamic light scattering: a practical guide and applications in biomedical sciences.

Abstract: Dynamic light scattering (DLS), also known as photon correlation spectroscopy (PCS), is a very powerful tool for studying the diffusion behaviour of macromolecules in solution. The diffusion coefficient, and hence the hydrodynamic radii calculated from it, depends on the size and shape of macromolecules. In this review, we provide evidence of the usefulness of DLS to study the homogeneity of proteins, nucleic acids, and complexes of protein–protein or protein–nucleic acid preparations, as well as to study protein–small molecule interactions. Further, we provide examples of DLS’s application both as a complementary method to analytical ultracentrifugation studies and as a screening tool to validate solution scattering models using determined hydrodynamic radii.

FAK in cancer: mechanistic findings and clinical applications

Abstract: Focal adhesion kinase (FAK) is a cytoplasmic protein tyrosine kinase that is overexpressed and activated in several advanced-stage solid cancers. FAK promotes tumour progression and metastasis through effects on cancer cells, as well as stromal cells of the tumour microenvironment. The kinase-dependent and kinase-independent functions of FAK control cell movement, invasion, survival, gene expression and cancer stem cell self-renewal. Small molecule FAK inhibitors decrease tumour growth and metastasis in several preclinical models and have initial clinical activity in patients with limited adverse events. In this Review, we discuss FAK signalling effects on both tumour and stromal cell biology that provide rationale and support for future therapeutic opportunities.

Colloidal Suspension Rheology

Abstract: 1. Introduction to colloid science and rheology 2. Hydrodynamic effects 3. Brownian hard spheres 4. Stable colloidal suspensions 5. Non-spherical particles 6. Weakly flocculated suspensions 7. Thixotropy 8. Shear thickening 9. Rheometry of suspensions 10. Suspensions in viscoelastic media 11. Advanced topics.