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991.
The differential ability of HLA B*5701+ long-term nonprogressors and progressors to restrict human immunodeficiency virus replication is not caused by loss of recognition of autologous viral gag sequences
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Migueles SA Laborico AC Imamichi H Shupert WL Royce C McLaughlin M Ehler L Metcalf J Liu S Hallahan CW Connors M 《Journal of virology》2003,77(12):6889-6898
Although the HLA B(*)5701 class I allele is highly overrepresented among human immunodeficiency virus (HIV)-infected long-term nonprogressors (LTNPs), it is also present at the expected frequency (11%) in patients with progressive HIV infection. Whether B57(+) progressors lack restriction of viral replication because of escape from recognition of highly immunodominant B57-restricted gag epitopes by CD8(+) T cells remains unknown. In this report, we investigate the association between restriction of virus replication and recognition of autologous virus sequences in 27 B(*)57(+) patients (10 LTNPs and 17 progressors). Amplification and direct sequencing of single molecules of viral cDNA or proviral DNA revealed low frequencies of genetic variations in these regions of gag. Furthermore, CD8(+) T-cell recognition of autologous viral variants was preserved in most cases. In two patients, responses to autologous viral variants were not demonstrable at one epitope. By using a novel technique to isolate primary CD4(+) T cells expressing autologous viral gene products, it was found that 1 to 13% of CD8(+) T cells were able to respond to these cells by gamma interferon production. In conclusion, escape-conferring mutations occur infrequently within immunodominant B57-restricted gag epitopes and are not the primary mechanism of virus evasion from immune control in B(*)5701(+) HIV-infected patients. Qualitative features of the virus-specific CD8(+) T-cell response not measured by current assays remain the most likely determinants of the differential abilities of HLA B(*)5701(+) LTNPs and progressors to restrict virus replication. 相似文献
992.
Jones AL Gane AM Herbert D Willey DL Rutter AJ Kille P Dancer JE Harwood JL 《Planta》2003,216(5):752-761
A beta-ketoacyl-acyl carrier protein (ACP) synthase III (KAS III; short-chain condensing enzyme) has been partly purified from pea leaves. The enzyme, which had acetyl-CoA:ACP acyltransferase (ACAT) activity, was resolved from a second, specific, ACAT protein. The KAS III enzyme had a derived molecular mass of 42 kDa (from its cDNA sequence) and operated as a dimer. Its enzymological characteristics were similar to those of two other plant KAS III enzymes except for its inhibition by thiolactomycin. A derivative of thiolactomycin containing a longer (C8 saturated) hydrophobic side-chain (compound 332) was a more effective inhibitor of pea KAS III and showed competitive inhibition towards malonyl-ACP whereas thiolactomycin showed uncompetitive characteristics at high concentrations. This difference may be due to the better fit of compound 332 into a hydrophobic pocket at the active site. A full-length cDNA for the pea KAS III was isolated. This was expressed in Escherichia coli as a fusion protein with glutathione S-transferase in order to facilitate subsequent purification. Demonstrated activity in preparations from E. coli confirmed that the cDNA encoded a KAS III enzyme. Furthermore, the expressed KAS III had ACAT activity, showing that the latter was inherent. The derived amino acid sequence of the pea cDNA showed 81-87% similarity to that for other plant dicotyledon KAS IIIs, somewhat less for Allium porrum (leek, 71%) and for Porphyra spp. (62%), Synechocystis spp. (65%) and various bacteria (42-65%). The pea KAS III exhibited four areas of homology, three of which were around the active-site Cys(123), His(323) and Asn(353). In addition, a stretch of 23 amino acids (residues 207-229 in the pea KAS III) was almost completely conserved in the plant KAS IIIs. Modelling this stretch showed they belonged to a peptide fragment that fitted over the active site and contained segments suggested to be involved in substrate binding and in conformational changes during catalysis, as well as an arginine suggested to participate in the acid-base catalytic mechanism. 相似文献
993.
Schwarzenbacher R Canaves JM Brinen LS Dai X Deacon AM Elsliger MA Eshaghi S Floyd R Godzik A Grittini C Grzechnik SK Guda C Jaroszewski L Karlak C Klock HE Koesema E Kovarik JS Kreusch A Kuhn P Lesley SA McMullan D McPhillips TM Miller MA Miller MD Morse A Moy K Ouyang J Robb A Rodrigues K Selby TL Spraggon G Stevens RC van den Bedem H Velasquez J Vincent J Wang X West B Wolf G Hodgson KO Wooley J Wilson IA 《Proteins》2003,53(1):142-145
994.
Fungal biology and agriculture: revisiting the field 总被引:1,自引:0,他引:1
Yarden O Ebbole DJ Freeman S Rodriguez RJ Dickman MB 《Molecular plant-microbe interactions : MPMI》2003,16(10):859-866
995.
996.
Cross GH Reeves AA Brand S Popplewell JF Peel LL Swann MJ Freeman NJ 《Biosensors & bioelectronics》2003,19(4):383-390
A new optical biosensor is described based on a dual waveguide interferometric technique. By addressing the waveguide structure with alternate polarisations the optogeometrical properties (density and thickness) of adsorbed protein layers at the sensor (solid)-liquid interface have been determined. Differences in the waveguide mode dispersion between the transverse electric (TE) and transverse magnetic (TM) modes allow unique solutions for adlayer thickness and refractive index to be determined at all stages during the formation process. The technique has been verified using standard protein systems and by comparing the data with published work using X-ray crystallography and neutron reflection techniques. The data obtained was found to be in excellent agreement with previously reported X-ray experiments given that typical film thicknesses for streptavidin layers were in the range 5.5-6.5 nm compared with the short axis crystal structure of between 4.8 and 5.6 nm. The precision of the measurements taken was of the order of 40 pm with respect to adsorbed adlayer thicknesses. This biosensor approach provides measurements of both thickness and density of adlayers to a high precision, simultaneously and in real time enabling detail of the structure and function of proteins to be elucidated. From such data it is possible to obtain information on the orientation, distortion and efficiency of immobilisation procedures as well as the interaction event of interest. The technique is expected to find utility with those interested in protein structure and function. This is an area of growing importance within the life sciences as the demand for quantitative analytical techniques increases with the growth in "proteomics". 相似文献
997.
Dacks JB Davis LA Sjögren AM Andersson JO Roger AJ Doolittle WF 《Proceedings. Biological sciences / The Royal Society》2003,270(Z2):S168-S171
Golgi bodies are nearly ubiquitous in eukaryotic cells. The apparent lack of such structures in certain eukaryotic lineages might be taken to mean that these protists evolved prior to the acquisition of the Golgi, and it raises questions of how these organisms function in the absence of this crucial organelle. Here, we report gene sequences from five proposed 'Golgi-lacking' organisms (Giardia intestinalis, Spironucleus barkhanus, Entamoeba histolytica, Naegleria gruberi and Mastigamoeba balamuthi). BLAST and phylogenetic analyses show these genes to be homologous to those encoding components of the retromer, coatomer and adaptin complexes, all of which have Golgi-related functions in mammals and yeast. This is, to our knowledge, the first molecular evidence for Golgi bodies in two major eukaryotic lineages (the pelobionts and heteroloboseids). This substantiates the suggestion that there are no extant primitively 'Golgi-lacking' lineages, and that this apparatus was present in the last common eukaryotic ancestor, but has been altered beyond recognition several times. 相似文献
998.
Heine A Canaves JM von Delft F Brinen LS Dai X Deacon AM Elsliger MA Eshaghi S Floyd R Godzik A Grittini C Grzechnik SK Guda C Jaroszewski L Karlak C Klock HE Koesema E Kovarik JS Kreusch A Kuhn P Lesley SA McMullan D McPhillips TM Miller MA Miller MD Morse A Moy K Ouyang J Page R Robb A Rodrigues K Schwarzenbacher R Selby TL Spraggon G Stevens RC van den Bedem H Velasquez J Vincent J Wang X West B Wolf G Hodgson KO Wooley J Wilson IA 《Proteins》2004,56(2):387-391
999.
Schwarzenbacher R Jaroszewski L von Delft F Abdubek P Ambing E Biorac T Brinen LS Canaves JM Cambell J Chiu HJ Dai X Deacon AM DiDonato M Elsliger MA Eshagi S Floyd R Godzik A Grittini C Grzechnik SK Hampton E Karlak C Klock HE Koesema E Kovarik JS Kreusch A Kuhn P Lesley SA Levin I McMullan D McPhillips TM Miller MD Morse A Moy K Ouyang J Page R Quijano K Robb A Spraggon G Stevens RC van den Bedem H Velasquez J Vincent J Wang X West B Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2004,55(3):768-771
1000.