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981.
Anton Skopin Alexey Shalygin Vladimir Vigont Olga ZiminaLyubov Glushankova Galina N. MozhayevaElena Kaznacheyeva 《Biochimie》2013
TRPC1 is a major component of store-operated calcium entry in many cell types. In our previous studies, three types of endogenous store-operated calcium channels have been described in HEK293 cells, but it remained unknown which of these channels are composed of TRPC1 proteins. Here, this issue has been addressed by performing single-channel analysis in HEK293 cells transfected with anti-TRPC1 siRNA (siTPRC1) or a TPRC1-encoding plasmid. The results show that thapsigargin-or agonist-induced calcium influx is significantly attenuated in siTRPC1-transfected HEK293 cells. TRPC1 knockdown by siRNA results in the disappearance of store-operated Imax channels, while the properties of Imin and INS channels are unaffected. In HEK293 cells with overexpressed TRPC1 protein, the unitary current–voltage relationship of exogenous TRPC1 channels is almost linear, with a slope conductance of about 17 pS. The extrapolated reversal potential of expressed TRPC1 channels is +30 mV. Therefore, the main electrophysiological and regulatory properties of expressed TRPC1 and native Imax channels are identical. Moreover, TRPC1 overexpression in HEK293 cells results in an increased number of store-operated Imax channels. All these data allow us to conclude that TRPC1 protein forms native store-operated Imax channels but is not an essential subunit for other store-operated channel types in HEK293 cells. 相似文献
982.
Alexey A. Malygin Olga A. Kossinova Ivan N. Shatsky Galina G. Karpova 《Nucleic acids research》2013,41(18):8706-8714
Previous analyses of complexes of 40S ribosomal subunits with the hepatitis C virus (HCV) internal ribosome entry site (IRES) have revealed contacts made by the IRES with ribosomal proteins. Here, using chemical probing, we show that the HCV IRES also contacts the backbone and bases of the CCC triplet in the 18S ribosomal RNA (rRNA) expansion segment 7. These contacts presumably provide interplay between IRES domain II and the AUG codon close to ribosomal protein S5, which causes a rearrangement of 18S rRNA structure in the vicinity of the universally conserved nucleotide G1639. As a result, G1639 becomes exposed and the corresponding site of the 40S subunit implicated in transfer RNA discrimination can select . These data are the first demonstration at nucleotide resolution of direct IRES–rRNA interactions and how they induce conformational transition in the 40S subunit allowing the HCV IRES to function without AUG recognition initiation factors. 相似文献
983.
984.
Vadim V. Mesyanzhinov Elena N. Peletskaya Viktor M. Zhdanov Alexander V. Efimov Alexey V. Finkelstein D. I. Ivanovsky 《Journal of biomolecular structure & dynamics》2013,31(2):447-458
Abstract On the basis of the secondary structure calculations from the known amino acid sequence we came to the conclusion that hepatitis A virus capsid proteins have the typical antiparallel beta-sheet bilayer structure. The predicted secondary structure of the HAV proteins can be well aligned with those of the poliovirus (type 1 Mahoney) and human rhinovirus (type 14). It enabled us to use the X-ray structure of the PV-1M and HRV-14 proteins as a template and then, firstly, to localize the positions of alpha and beta regions in the architecture of the HAV protein molecules and, secondly, to discover the amino acid homologies of the secondary structure regions aligned. The obtained model of the three-dimensional structure for HAV proteins helped us to indicate the exposed regions of the polypeptide chains and to pinpoint the potential neutralizing antigenic sites. 相似文献
985.
Abstract A general methodology is proposed for the conformational modelling of biomolecular systems. The approach allows one: (i) to describe the system under investigation by an arbitrary set of internal variables, i.e., torsion angles, bond angles, and bond lengths; it offers a possibility to pass from the free structure to a completely fixed one with the number of variables from 3N to zero, respectively, where N is the number of atoms; (ii) to consider both, a single molecule and a complex of many molecules, (e.g., proteins, water, ligands, etc.) in terms of one universal model; (iii) to study the dynamics of the system using explicit analytical Lagrangian equations of motion, thus opening up possibilities for investigations of slow concerted motions such as domain oscillations in proteins etc.; (iv) to calculate the partial derivatives of various functions of conformation, e.g., the conformatinal energy or external constraints imposed, using a standard efficient procedure regardless of the variables and the structure of the system. The approach is meant to be used in various investigations concerning the conformations and dynamics of biomacromolecules. 相似文献
986.
Alexey G. Krushelnitsky Vladimir D. Fedotov Jiri Spevacek Jaroslav Straka 《Journal of biomolecular structure & dynamics》2013,31(2):211-224
Abstract Temperature dependencies of 1H non-selective NMR T1 and T2 relaxation times measured at two resonance frequencies and natural abundance l3C NMR relaxation times Tl and Tlr measured at room temperature have been studied in a set of dry and wet solid proteins—;Bacterial RNase, lysozyme and Bovine serum albumin (BSA). The proton and carbon data were interpreted in terms of a model supposing three kinds of internal motions in a protein. These are rotation of the methyl protons around the axis of symmetry of the methyl group, and fast and slow oscillations of all atoms. The correlation times of these motions in solid state are found around 10?11, 10?9 and 10?6 s, respectively. All kinds of motion are characterized by the inhomogeneous distribution of the correlation times. The protein dehydration affects only the slow internal motion. The amplitude of the slow motion obtained from the carbon data is substantially less than that obtained from the proton data. This difference can be explained by taking into account different relative inter- and intra- chemical group contributions to the proton and carbon second moments. The comparison of the solid state and solution proton relaxation data showed that the internal protein dynamics in these states is different: the slow motion seems to be few orders of magnitude faster in solution. 相似文献
987.
Oxana V. Galzitskaya Michael Yu. Lobanov Alexey V. Finkelstein 《Journal of biomolecular structure & dynamics》2013,31(4):595-598
Abstract Mastoparan B (MP-B) is an antimicrobial cationic tetradecapeptide amide isolated from the venom of the hornet Vespa basalis. NMR spectroscopy was used to study the membrane associated structures of MP-B in various model membrane systems such as 120 mM DPC micelles, 200 mM SDS micelles, and 3%(w/v) DMPC/DHPC (1:2) bicelles. In all systems, MP-B has an amphiphilic α-helical structure from Lys2 to Leu14. NOESY experiments performed on MP-B in nondeuterated SDS micelles show that protons in the indole ring of Trp9 are in close contact with methylene protons of SDS micelles. T1 relaxation data and NOE data revealed that the bound form of MP-B may be dominant in SDS micelles. The interactions between MP-B and zwitterionic DPC micelles were much weaker than those between MP-B and anionic SDS micelles. By substitution of Trp9 with Ala9, the pore-forming activity of MP-B was decreased dramatically. All of these results imply that strong electrostatic interactions between the positively charged Lys residues in MP-B and the anionic phospholipid head groups must be the primary factor for MP-B binding to the cell membrane. Then, insertion of the indole ring of Trp9 into the membrane, as well as the amphiphilic α-helical structures of MP-B may allow MP-B to span the lipid bilayer through the C-terminal portion. These structural features are crucial for the potent antibiotic activities of MP-B. 相似文献
988.
989.
Simran K. Jandu Alanah K. Webb Alina Pak Baris Sevinc Daniel Nyhan Alexey M. Belkin Nicholas A. Flavahan Dan E. Berkowitz Lakshmi Santhanam 《Amino acids》2013,44(1):261-269
The multifunctional enzyme tissue transglutaminase (TG2) contributes to the development and progression of several cardiovascular diseases. Extracellular rather than intracellular TG2 is enzymatically active, however, the mechanism by which it is exported out of the cell remains unknown. Nitric oxide (NO) is shown to constrain TG2 externalization in endothelial and fibroblast cells. Here, we examined the role of both exogenous and endogenous (endothelial cell-derived) NO in regulating TG2 localization in vascular cells and tissue. NO synthase inhibition in endothelial cells (ECs) using N-nitro l-arginine methyl ester (l-NAME) led to a time-dependent decrease in S-nitrosation and increase in externalization of TG2. Laminar shear stress led to decreased extracellular TG2 in ECs. S-nitrosoglutathione treatment led to decreased activity and externalization of TG2 in human aortic smooth muscle and fibroblast (IMR90) cells. Co-culture of these cells with ECs resulted in increased S-nitrosation and decreased externalization and activity of TG2, which was reversed by l-NAME. Aged Fischer 344 rats had higher tissue scaffold-associated TG2 compared to young. NO regulates intracellular versus extracellular TG2 localization in vascular cells and tissue, likely via S-nitrosation. This in part, explains increased TG2 externalization and activity in aging aorta. 相似文献
990.
Kwame Amaning Maryse Lowinski Francois Vallee Valerie Steier Christophe Marcireau Antonio Ugolini Cecile Delorme Frédéric Foucalt Gary McCort Nathalie Derimay Cyrielle Andouche Stephanie Vougier Sylvie Llopart Nis Halland Alexey Rak 《Bioorganic & medicinal chemistry letters》2013,23(12):3620-3626
We report the analysis of an in-house fragment screening campaign for the oncology target MEK1. The application of virtual screening (VS) as a primary fragment screening approach, followed by biophysical validation using differential screening fluorimetry (DSF), with resultant binding mode determination by X-ray crystallography (X-ray), is presented as the most time and cost-effective combination of in silico and in vitro methods to identify fragments. We demonstrate the effectiveness of the VS–DSF workflow for the early identification of fragments to both ‘jump-start’ the drug discovery project and to complement biochemical screening data. 相似文献