Spin label EPR structural studies of the N-terminus of α-spectrin

AbstractSpectrin, a vital component in human erythrocyte, is composed of α- and β-subunits, which associate to form (αβ)2 tetramers. The tetramerization site is believed to involve the α-spectrin N-terminus and the β-spectrin C-terminus. Abnormal interactions in this region may lead to blood disorders. It has been proposed that both termini consist of partial structural domains and that tetramerization involves the association of these partial domains. We have studied the N-terminal region of a model peptide for α-spectrin by making a series of double spin-labeled peptides and studying their dipolar interaction by electron paramagnetic resonance methods. Our results indicate that residues 21–42 of the N-terminus region exhibit an α-helical conformation, even in the absence of β-spectrin

Computational Study of the Human Dystrophin Repeats: Interaction Properties and Molecular Dynamics

Dystrophin is a large protein involved in the rare genetic disease Duchenne muscular dystrophy (DMD). It functions as a mechanical linker between the cytoskeleton and the sarcolemma, and is able to resist shear stresses during muscle activity. In all, 75% of the dystrophin molecule consists of a large central rod domain made up of 24 repeat units that share high structural homology with spectrin-like repeats. However, in the absence of any high-resolution structure of these repeats, the molecular basis of dystrophin central domain's functions has not yet been deciphered. In this context, we have performed a computational study of the whole dystrophin central rod domain based on the rational homology modeling of successive and overlapping tandem repeats and the analysis of their surface properties. Each tandem repeat has very specific surface properties that make it unique. However, the repeats share enough electrostatic-surface similarities to be grouped into four separate clusters. Molecular dynamics simulations of four representative tandem repeats reveal specific flexibility or bending properties depending on the repeat sequence. We thus suggest that the dystrophin central rod domain is constituted of seven biologically relevant sub-domains. Our results provide evidence for the role of the dystrophin central rod domain as a scaffold platform with a wide range of surface features and biophysical properties allowing it to interact with its various known partners such as proteins and membrane lipids. This new integrative view is strongly supported by the previous experimental works that investigated the isolated domains and the observed heterogeneity of the severity of dystrophin related pathologies, especially Becker muscular dystrophy

Product innovation and population dynamics in the German insurance market

Empirical research in organizational ecology has mainly focused on analyzing founding and mortality rates using life history data of the organizations. We try to extend this approach in our study in a number of ways. In contrast to most empirical studies in organizational ecology, we chose a population of service organizations, in particular the German insurance companies, the development dynamics of which are rather obvious in the innovative activities of existing organizations than in founding activities. We further discuss the points of contact between the organizational ecology approach and the theory of industry life cycles and extend the analysis to the relationship between innovative activities and population dynamics. The study examines the effects of population density, former events, and organizational size and age structure in the population of property & casualty insurance companies on the number of product innovations generated. We will further develop a concept for an insurance specific industry life cycle with a non-typical maturation and degeneration phase