38 research outputs found
The Terminal Immunoglobulin-Like Repeats of LigA and LigB of Leptospira Enhance Their Binding to Gelatin Binding Domain of Fibronectin and Host Cells
Leptospira spp. are pathogenic spirochetes that cause the zoonotic disease leptospirosis. Leptospiral immunoglobulin (Ig)-like protein B (LigB) contributes to the binding of Leptospira to extracellular matrix proteins such as fibronectin, fibrinogen, laminin, elastin, tropoelastin and collagen. A high-affinity Fn-binding region of LigB has been localized to LigBCen2, which contains the partial 11th and full 12th Ig-like repeats (LigBCen2R) and 47 amino acids of the non-repeat region (LigBCen2NR) of LigB. In this study, the gelatin binding domain of fibronectin was shown to interact with LigBCen2R (KDâ=â1.91±0.40 ”M). Not only LigBCen2R but also other Ig-like domains of Lig proteins including LigAVar7'-8, LigAVar10, LigAVar11, LigAVar12, LigAVar13, LigBCen7'-8, and LigBCen9 bind to GBD. Interestingly, a large gain in affinity was achieved through an avidity effect, with the terminal domains, 13th (LigA) or 12th (LigB) Ig-like repeat of Lig protein (LigAVar7'-13 and LigBCen7'-12) enhancing binding affinity approximately 51 and 28 fold, respectively, compared to recombinant proteins without this terminal repeat. In addition, the inhibited effect on MDCKs cells can also be promoted by Lig proteins with terminal domains, but these two domains are not required for gelatin binding domain binding and cell adhesion. Interestingly, Lig proteins with the terminal domains could form compact structures with a round shape mediated by multidomain interaction. This is the first report about the interaction of gelatin binding domain of Fn and Lig proteins and provides an example of Lig-gelatin binding domain binding mediating bacterial-host interaction
Expression of osterix Is Regulated by FGF and Wnt/ÎČ-Catenin Signalling during Osteoblast Differentiation
Osteoblast differentiation from mesenchymal cells is regulated by multiple signalling pathways.
Here we have analysed the roles of Fibroblast Growth Factor (FGF) and canonical
Wingless-type MMTV integration site (Wnt/ÎČ-Catenin) signalling pathways on zebrafish
osteogenesis. We have used transgenic and chemical interference approaches to manipulate
these pathways and have found that both pathways are required for osteoblast differentiation
in vivo. Our analysis of bone markers suggests that these pathways act at the same
stage of differentiation to initiate expression of the osteoblast master regulatory gene osterix
(osx). We use two independent approaches that suggest that osx is a direct target of these
pathways. Firstly, we manipulate signalling and show that osx gene expression responds
with similar kinetics to that of known transcriptional targets of the FGF and Wnt pathways.
Secondly, we have performed ChIP with transcription factors for both pathways and our
data suggest that a genomic region in the first intron of osx mediates transcriptional activation.
Based upon these data, we propose that FGF and Wnt/ÎČ-Catenin pathways act in part
by directing transcription of osx to promote osteoblast differentiation at sites of bone
formation
Crystal, Solution and In silico Structural Studies of Dihydrodipicolinate Synthase from the Common Grapevine
Dihydrodipicolinate synthase (DHDPS) catalyzes the rate limiting step in lysine biosynthesis in bacteria and plants. The structure of DHDPS has been determined from several bacterial species and shown in most cases to form a homotetramer or dimer of dimers. However, only one plant DHDPS structure has been determined to date from the wild tobacco species, Nicotiana sylvestris (Blickling et al. (1997) J. Mol. Biol. 274, 608â621). Whilst N. sylvestris DHDPS also forms a homotetramer, the plant enzyme adopts a âback-to-backâ dimer of dimers compared to the âhead-to-headâ architecture observed for bacterial DHDPS tetramers. This raises the question of whether the alternative quaternary architecture observed for N. sylvestris DHDPS is common to all plant DHDPS enzymes. Here, we describe the structure of DHDPS from the grapevine plant, Vitis vinifera, and show using analytical ultracentrifugation, small-angle X-ray scattering and X-ray crystallography that V. vinifera DHDPS forms a âback-to-backâ homotetramer, consistent with N. sylvestris DHDPS. This study is the first to demonstrate using both crystal and solution state measurements that DHDPS from the grapevine plant adopts an alternative tetrameric architecture to the bacterial form, which is important for optimizing protein dynamics as suggested by molecular dynamics simulations reported in this study
Megascopic Quantum Phenomena. A Critical Study of Physical Interpretations
A megascopic revalidation is offered providing responses and resolutions of
current inconsistencies and existing contradictions in present-day quantum
theory. As the core of this study we present an independent proof of the
Goldstone theorem for a quantum field formulation of molecules and solids.
Along with phonons two types of new quasiparticles appear: rotons and
translons. In full analogy with Lorentz covariance, combining space and time
coordinates, a new covariance is necessary, binding together the internal and
external degrees of freedom, without explicitly separating the centre-of-mass,
which normally applies in both classical and quantum formulations. The
generally accepted view regarding the lack of a simple correspondence between
the Goldstone modes and broken symmetries, has significant consequences: an
ambiguous BCS theory as well as a subsequent Higgs mechanism. The application
of the archetype of the classical spontaneous symmetry breaking, i.e. the
Mexican hat, as compared to standard quantum relations, i.e. the Jahn-Teller
effect, superconductivity or the Higgs mechanism, becomes a disparity. In
short, symmetry broken states have a microscopic causal origin, but transitions
between them have a teleological component. The different treatments of the
problem of the centre of gravity in quantum mechanics and in field theories
imply a second type of Bohr complementarity on the many-body level opening the
door for megascopic representations of all basic microscopic quantum axioms
with further readings for teleonomic megascopic quantum phenomena, which have
no microscopic rationale: isomeric transitions, Jahn-Teller effect, chemical
reactions, Einstein-de Haas effect, superconductivity-superfluidity, and
brittle fracture.Comment: 117 pages, 17 sections, final revised version from 20 May 2019 but
uploaded after the DOI was know
Minkowskiâs Modern World
International audienceIn this paper I want to suggest that much of the excitement generated by Hermann Minkowskiâs lecture ââRaum und Zeitââ among scientists and philosophers arose from an idea that was scandalous when announced on September 21, 1908, but which was soon assimilated, first by theorists and then by the scientific community at large: Euclidean geometry was no longer adequate to the task of describing physical reality, and had to be replaced by the geometry of a four-dimensional space Minkowski called the ââworld.ââ Such an affirmation engaged implicitly with the Riemann-Helmholtz-Lie-PoincarĂ© problem of space, and flatly contradicted PoincarĂ©âs conventionalist philosophy, whereby the geometry assigned to physical space is a matter of choice, not necessity