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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
2.
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
3.
We have analyzed a total of 12 different global and local multiple
protein-sequence alignment methods. The purpose of this study is to
evaluate each method's ability to correctly identify the ordered series of
motifs found among all members of a given protein family. Four
phylogenetically distributed sets of sequences from the hemoglobin, kinase,
aspartic acid protease, and ribonuclease H protein families were used to
test the methods. The performance of all 12 methods was affected by (1) the
number of sequences in the test sets, (2) the degree of similarity among
the sequences, and (3) the number of indels required to produce a multiple
alignment. Global methods generally performed better than local methods in
the detection of motif patterns.
相似文献
4.
In vitro stimulation of alkaline phosphatase activity in immature embryonic chick pelvic cartilage by adenosine 下载免费PDF全文
Cyclic AMP content in embryonic chick pelvic cartilage increases significantly as the embryo ages from 8 to 10 d. This in ovo elevation in cyclic AMP content precedes maximal cartilage alkaline phosphatase activity by some 24 h. We studied whether this temporal relationship may be causally related, using an in vitro organ culture. Incubation of pelvic cartilage from 9- and 10-d embryos in medium containing monobutyryl cyclic AMP (BtcAMP) resulted in significant increases in alkaline phosphatase activity (220 and 66 percent, respectively) as compared to that of cartilages incubated in medium alone. This stimulation was both concentration- and time-dependent with maximal response at 0.5 mM BtcAMP and 4-h incubation, respectively. Similar incubations of cartilage in medium containing 1-methyl-3-isobutyl xanthine (MIX), 0.25 mM, also resulted in increased alkaline phosphatase activity (114 percent). However, pelvic cartilage from 11-d embryos incubated in medium containing BtcAMP or MIX showed no increase in alkaline phosphatase activity. We postulated that developmental age was the factor responsible for this difference in response and that immature cartilage (that with little or no alkaline phosphatase activity) would respond to BtcAMP whereas mature cartilage (that with significant alkaline phosphatase activity) would not. This was tested by incubating end sections of 11-d cartilage, which have little alkaline phosphatase activity, and center sections, which have significantly alkaline phosphatase activity, with both BtcAMP and MIX. Alkaline phosphatase activity in end sections (immature cartilage) was stimulated by BtcAMP and MIX, whereas it was not stimulated in the center sections. Actinomycin D and cycloheximide inhibited BtcAMP and MIX stimulation of alkaline phosphatase activity. Thus, the in vitro data suggest that cyclic AMP is a mediator for the stimulation of alkaline phosphatase activity in embryonic cartilage. 相似文献
5.
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
6.
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
7.
Orienting rigid and flexible biological assemblies in ferrofluids for small-angle neutron scattering studies 下载免费PDF全文
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
8.
Isolation and characterization of acetylated histones H3 and H4 and their assembly into nucleosomes 总被引:5,自引:0,他引:5
Nucleosome and chromatin structure/function relationships of histone acetylations are not understood. To address these questions we have developed chromatographic procedures that separate subtypes of H3 and the acetylated states of histone H3 and H4 in exceptionally pure forms. The sites of acetylation of the intermediately acetylated states of H3 have been determined and show a specific pattern of acetylation. An unexpected finding was the identification of a fifth site of acetylation in H3 at lysine 27. Nucleosome particles with fully acetylated H3 and H4 have been assembled on the Lytechinus variegatus 5 S rRNA DNA phasing sequence and characterized. These defined acetylated H3 and H4 particles migrate more slowly in polyacrylamide nucleoprotein particle gels than the control particles indicating a subtle effect of acetylation in nucleosome structure. However, DNA footprinting of these particles using DNase I show only small changes when compared to control particles over the core particle DNA length. It is shown further that H3 cysteines in the particle containing fully acetylated H3 and H4 were not accessible to iodoacetamide indicating that protein factors additional to H3 and H4 acetylation are required to make H3 cysteines accessible to the label. These findings are consistent with the proposal that histones H3, H4 acetylations exert their major effects outside of the core particle 146-base pair DNA, either on the DNA segment entering and leaving the nucleosome or possibly on the internucleosome interactions that involve the amino-terminal domains of the core histones in organization and stability of higher order chromatin structures. 相似文献
9.
10.
Northeast Red Beans Produce a Thermostable and pH-Stable Defensin-Like Peptide with Potent Antifungal Activity 总被引:1,自引:0,他引:1
A 5.4-kDa antifungal peptide was purified from Phaseolus vulgaris L. cv. “northeast red bean” using a protocol that entailed affinity chromatography, ion exchange chromatography, and gel filtration. The molecular mass was determined by matrix-assisted laser desorption ionization time-of-flight. The N-terminal amino acid sequence of the peptide was highly homologous to defensins and defensin-like peptides from several plant species. The peptide impeded the growth of a number of pathogenic fungi, including Mycosphaerella arachidicola Khokhr. (IC50 = 1.7 μM), Setosphaeria turcica Luttr., Fusarium oxysporum Schltdl., and Valsa mali Miyabe & G. Yamada. Antifungal activity of the peptide was fully preserved at temperatures up to 100 °C and pH values from 0 to 12. Congo red deposition at the hyphal tip of M. arachidicola was detected after exposure to the peptide, signifying that the peptide had suppressed hyphal growth. The antifungal peptide did not manifest antiproliferative activity toward human breast cancer MCF7 cells and hepatoma HepG2 cells, in contradiction to the bulk of previously reported plant defensins. The data suggest distinct structural requirements for antifungal and antiproliferative activities. 相似文献