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1.
The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid-state NMR spectra, conformation-dependent 15N and 13C NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide 1H nuclei, and quantitative measurements of site-specific 15N–15N dipole–dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that structures of the N-terminal domain (NTD) and the C-terminal domain (CTD) observed in solution are largely retained. However, specific segments, including the N-terminal β-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD–CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 310-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD–CTD interface, while structural variations within NTD hexamers, around local 3-fold symmetry axes, and in CTD–CTD dimerization interfaces are less significant. 相似文献
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Michèle Ramsay Stephen T. Reeders Peter D. Thomson Lawrence S. Milner L. Lazarou Thomas M. Barratt Adrian Yau Ordan J. Lehmann Trefor Jenkins 《Human genetics》1988,79(1):73-75
Summary The autosomal dominant form of polycystic kidney disease (ADPKD) has been linked to the -globin gene locus on 16p. Linkage studies between the autosomal recessive type (ARPKD) and the 3 HVR of the -globin gene cluster showed that the ARPKD and ADPKD are not allelic. 相似文献
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Effects of low-chloride solutions on action potentials of sheep cadiac purkinje fibers 总被引:2,自引:0,他引:2
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The rapid repolarization during phase 1 of the action potential of sheep cardiac purkinje fibers has been attributed to a time- and voltage-dependent chloride current. In part, this conclusion was based on experiments that showed a substantial slowing of phase 1 when larger, presumably impermeant, anions were substituted for chloride in tyrode’s solution. We have re- examined the electrical effects of low-chloride solutions. We recorded action potentials of sheep cardiac purkinje fibers in normal tyrode’s solution and in low-chloride solutions made by substituting sodium propionate, acetylglycinate, methylsulfate, or methanesulfonate for the NaCl of Tyrode’s solution. Total calcium was adjusted to keep calcium ion activity of test solutions equal to that of control solutions. Propionate gave qualitatively variable results in preliminary experiments; it was not tested further. Low-chloride solutions made with the other anions gave much more consistent results: phase 1 and the notch that often occurs between phases 1 and 2 were usually unaffected, and the action potential duration usually increased. The only apparent change in the resting potential was a transient 3-6 mV depolarization when low-chloride solution was first admitted to the chamber, and a symmetrical transient hyperpolarization when chloride was returned to normal. If a time- and voltage-dependent chloride current exists in sheep cardiac purkinje fibers, our results suggest that it plays little role in generating phase 1 of the action potential. 相似文献
6.
Wu-Nan Wen Tai-Lin Lieu Huei-Jane Chang Sheng Wang Wuu Mei-Ling Yau K. Y. Jan 《Human genetics》1981,59(3):201-203
Summary A significantly higher frequency of baseline sister chromatid exchange (SCE) was found in the cultured lymphocytes of 13 Blackfoot disease patients (BFP) in comparison with that of healthy persons (HP). Twelve of these BFP consumed well water containing a high concentration of arsenic for 15 years or longer and had switched to drinking tap water 12 years before the time of this study. Sodium arsenite was found to be effective in increasing the SCE frequency and delaying the cell growth of the lymphocytes from both BFP and HP. However, the SCE increment induced by sodium arsenite as well as the progression of the cell divisions in the cultured lymphocytes showed no significant difference between BFP and HP. 相似文献
7.
P M Yau T Godefroy-Colburn C H Birge T V Ramabhadran R E Thach 《Journal of virology》1978,27(3):648-658
Inhibitors of elongation steps in protein synthesis such as cycloheximide and anisomycin mimic interferon treatment in that they specifically inhibit the synthesis of certain viral proteins. These specific effects are seen only at very low concentrations of the antibiotics, under conditions where host cellular protein synthesis, as well as cell viability, are not severely reduced. A qualitatively as well as quantitatively close correlation between the effects of the two types of agents has been established for encephalomyocarditis virus, vesicular stomatitis virus and murine leukemia virus protein synthesis. It is concluded that one of the primary mechanisms of interferon action may be a nonspecific retardation of one or more elongation steps, and that this may be sufficient to account for its effects on the replication of certain viruses such as encephalomyocarditis and vesicular stomatitis viruses. 相似文献
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Orienting rigid and flexible biological assemblies in ferrofluids for small-angle neutron scattering studies
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![点击此处可从《Biophysical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
T. Sosnick S. Charles G. Stubbs P. Yau E. M. Bradbury P. Timmins J. Trewhella 《Biophysical journal》1991,60(5):1178-1189
Small-angle scattering from macromolecules in solution is widely used to study their structures, but the information content is limited because the molecules are generally randomly oriented and hence the data are spherically averaged. The use of oriented rodlike structures for scattering, as in fiber diffraction, greatly increases the amount of structural detail that can be obtained. A new technique using a ferromagnetic fluid has been developed to align elongated structures independent of their intrinsic magnetic properties. This technique is ideal for small-angle neutron scattering because the scattering from the ferrofluid particles can be reduced significantly by matching the neutron scattering length density of the particles to a D2O solvent (“contrast matching”). The net result is scattering primarily from the ordered biological assembly in a solution environment that can be adjusted to physiological pH and ionic strength. Scattering results from ordered tobacco mosaic virus, tobacco rattle virus, and chromain fibers are presented. 相似文献