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991.
F Revah D Bertrand J L Galzi A Devillers-Thiéry C Mulle N Hussy S Bertrand M Ballivet J P Changeux 《Nature》1991,353(6347):846-849
A variety of ligand-gated ion channels undergo a fast activation process after the rapid application of agonist and also a slower transition towards desensitized or inactivated closed channel states when exposure to agonist is prolonged. Desensitization involves at least two distinct closed states in the acetylcholine receptor, each with an affinity for agonists higher than those of the resting or active conformations. Here we investigate how structural elements could be involved in the desensitization of the acetylcholine-gated ion channel from the chick brain alpha-bungarotoxin sensitive homo-oligomeric alpha 7 receptor, using site-directed mutagenesis and expression in Xenopus oocytes. Mutations of the highly conserved leucine 247 residue from the uncharged MII segment of alpha 7 suppress inhibition by the open-channel blocker QX-222, indicating that this residue, like others from MII, faces the lumen of the channel. But, unexpectedly, the same mutations decrease the rate of desensitization of the response, increase the apparent affinity for acetylcholine and abolish current rectification. Moreover, unlike wild-type alpha 7, which has channels with a single conductance level, the leucine-to-threonine mutant has an additional conducting state active at low acetylcholine concentrations. It is possible that mutation of Leu 247 renders conductive one of the high-affinity desensitized states of the receptor. 相似文献
992.
A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa. 总被引:59,自引:0,他引:59
G J Farrar P Kenna S A Jordan R Kumar-Singh M M Humphries E M Sharp D M Sheils P Humphries 《Nature》1991,354(6353):478-480
The group of retinopathies termed retinitis pigmentosa (RP) greatly contribute to visual dysfunction in man with a frequency of roughly 1 in 4,000. We mapped the first autosomal dominant RP (adRP) gene to chromosome 3q, close to the gene encoding rhodopsin, a rod photoreceptor pigment protein. Subsequently, mutations in this gene have been implicated as responsible for some forms of adRP. Another adRP gene has been mapped to chromosome 8p. A third adRP gene in a large Irish pedigree has been mapped to chromosome 6p, showing tight linkage with the gene for peripherin, a photoreceptor cell-specific glycoprotein, which is thus a strong candidate for the defective gene. We have now identified a three-base-pair deletion which results in the loss of one of a pair of highly conserved cysteine residues in the predicted third transmembrane domain of peripherin. This deletion segregates with the disease phenotype but is not present in unaffected controls, and suggests that mutant peripherin gives rise to retinitis pigmentosa. 相似文献
993.
High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. 总被引:90,自引:0,他引:90
Nerve growth factor (NGF) interacts with two different low-affinity receptors that can be distinguished by affinity crosslinking. Reconstitution experiments by membrane fusion and transient transfection into heterologous cells indicate that high-affinity NGF binding requires coexpression and binding to both the low-affinity NGF receptor and the tyrosine kinase trk gene product. These studies reveal a new growth factor receptor-mediated mechanism of cellular differentiation involving trk and the low-affinity NGF receptor. 相似文献
994.
In Drosophila simulans in California, an inherited cytoplasmic incompatibility factor reduces egg hatch when infected males mate with uninfected females. The infection is spreading at a rate of more than 100 km per year; populations in which the infection was rare have become almost completely infected within three years. Analyses of the spread using estimates of selection in the field suggest dispersal distances far higher than those found by direct observation of flies. Hence, occasional long-distance dispersal, possibly coupled with local extinction and recolonization, may be important to the dynamics. Incompatibility factors that can readily spread through natural populations may be useful for population manipulation and important as a post-mating isolating mechanism. 相似文献
995.
996.
A coat subunit of Golgi-derived non-clathrin-coated vesicles with homology to the clathrin-coated vesicle coat protein beta-adaptin 总被引:76,自引:0,他引:76
T Serafini G Stenbeck A Brecht F Lottspeich L Orci J E Rothman F T Wieland 《Nature》1991,349(6306):215-220
Four high-molecular-weight proteins form the main subunits of the coat of Golgi-derived (non-clathrin) coated vesicles. One of these coat proteins, beta-COP, is identical to a Golgi-associated protein of relative mass 110,000 (110K) that shares homology with the adaptin proteins of clathrin-coated vesicles. This connection, and the comparable molecular weights of the coat proteins of Golgi-derived and clathrin-coated vesicles, indicates that they may be structurally related. The identification of beta-COP as the 110K protein explains the blocking of secretion by the drug brefeldin A. 相似文献
997.
New use of BCG for recombinant vaccines 总被引:147,自引:0,他引:147
C K Stover V F de la Cruz T R Fuerst J E Burlein L A Benson L T Bennett G P Bansal J F Young M H Lee G F Hatfull 《Nature》1991,351(6326):456-460
BCG, a live attenuated tubercle bacillus, is the most widely used vaccine in the world and is also a useful vaccine vehicle for delivering protective antigens of multiple pathogens. Extrachromosomal and integrative expression vectors carrying the regulatory sequences for major BCG heat-shock proteins have been developed to allow expression of foreign antigens in BCG. These recombinant BCG strains can elicit long-lasting humoral and cellular immune responses to foreign antigens in mice. 相似文献
998.
999.
A pseudoknot-like structure required for efficient self-cleavage of hepatitis delta virus RNA 总被引:41,自引:0,他引:41
Hepatitis delta virus genomic and antigenomic RNAs contain a self-cleavage site hypothesized to function in processing the viral RNA during replication. Self-cleavage requires only a divalent cation and is mediated at the genomic site by a sequence of less than 85 nucleotides. We propose that the genomic self-cleaving sequence element and a corresponding sequence from the anti-genomic RNA could generate related secondary structures. The region of the antigenomic sequence, predicted from the proposed structure, was synthesized and shown to be sufficient for self-cleavage. Evidence for two stems which form a tertiary interaction was obtained by site-specific mutagenesis of the antigenomic sequence. Efficient self-cleavage in 10 M formamide or 5 M urea, also a property of the genomic sequence, was dependent on base-pairing in both stems. But in the absence of denaturants, the stem distal to the site of cleavage was not required, suggesting that the tertiary interaction stabilizes the structure required for self-cleavage. 相似文献
1000.
Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1 总被引:135,自引:0,他引:135
L Pevny M C Simon E Robertson W H Klein S F Tsai V D'Agati S H Orkin F Costantini 《Nature》1991,349(6306):257-260