Mal de Meleda is an autosomal recessive palmoplantar keratoderma associated with mutations in a gene encoding SLURP-1. SLURP-1 controls growth, differentiation, and apoptosis of keratinocytes by interaction with α7-type nicotinic acetylcholine receptors. SLURP-1 has a three-finger structure with a β-structural core (head) and three prolonged loops (fingers). To determine the role of SLURP-1 mutations, we produced 22 mutant variants of the protein, including those involved in Mal de Meleda pathogenesis. All mutants except R71H, R71P, T52A, R96P, and L98P were produced in the folded form. SLURP-1 reduces the growth of Het-1A keratinocytes; thus, we studied the influence of the mutations on its antiproliferative activity. Mutations in loops I and III led to the protein inactivation, whereas most mutations in loop II increased SLURP-1 antiproliferative activity. Alanine substitutions of R96 and L98 residues located in the protein head resulted in the appearance of additional pro-apoptotic activity. Our results agree with the diversity of Mal de Meleda phenotypes. Using obtained functional data, the SLURP-1/α7 type nicotinic acetylcholine receptor complex was modeled in silico. Our study provides functional and structural information about the role of the SLURP-1 mutations in Mal de Meleda pathogenesis and predicts SLURP-1 variants, which could drive the disease.
This work continues the previous study and is aimed at designing a more efficient ligand for α 7 nAChR using α ?conotoxin PnIA. Here, we applied the computational protein surface topography (PST) technique, developed at the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, and for the first time used it to select the necessary mutations in conotoxins.
Set out the process of preparation and holding of computer modeling of digital devices on-Board equipment of space vehicles. These digital devices are protected from the risk of dielectric printed sites ESD, as a result of internal electrified, high conductivity of a dielectric - nano conductivity. A distinctive feature of the proposed process modeling is the count of nano conductivity dielectric printed sites on the parameters of the digital device.
The aim objective of SMMS2015 is to present the latest research and results of scientists related to Simulation, Modelling and Mathematical Statistics topics. This conference provided opportunities for the different areas delegates to exchange new ideas and application experiences face to face, to establish business or research relations and to find global partners for future collaboration.