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51.
HYPERKALAEMIC periodic paralysis (HYPP) is an autosomal dominant disease that results in episodic electrical inexcitability and paralysis of skeletal muscle. Electrophysiological data indicate that tetrodotoxin-sensitive sodium channels from muscle cells of HYPP-affected individuals show abnormal inactivation. Genetic analysis of nine HYPP families has shown tight linkage between the adult skeletal muscle sodium channel alpha-subunit gene on chromosome 17q and the disease (lod score, z = 24; recombination frequency 0 = 0), strongly suggesting that mutations of the alpha-subunit gene cause HYPP. We sequenced the alpha-subunit coding region isolated from muscle biopsies from affected (familial HYPP) and control individuals by cross-species polymerase chain reaction-mediated complementary DNA cloning. We have identified an A----G substitution in the patient's messenger RNA that causes a Met----Val change in a highly conserved region of the alpha-subunit, predicted to be in a transmembrane domain. This same change was found in a sporadic case of HYPP as a new mutation. We have therefore discovered a voltage-gated channel mutation responsible for a human genetic disease. 相似文献
52.
Idealization of the hydrophobic segment of the alkaline phosphatase signal peptide 总被引:10,自引:0,他引:10
Proteins secreted by prokaryotic cells are synthesized as precursors containing an amino-terminal extension sequence or signal peptide. Although these signal peptides share little primary sequence homology, recent studies suggest that they function via common pathways during the transport process and that a common element may reside in their secondary structural characteristics. We are investigating the role of an idealized hydrophobic sequence with high potential for alpha-helix formation in the Escherichia coli alkaline phosphatase signal peptide. Here, amino-acid substitutions were made using site-directed mutagenesis to produce a mutant signal sequence containing nine consecutive leucine residues in the hydrophobic core segment. Transport studies with this mutant precursor indicate that mature alkaline phosphatase is correctly targeted to the E. coli periplasm and that processing of the precursor to the mature form of the enzyme is extremely rapid. In contrast, processing is slowed when the mutant signal sequence is lengthened by the insertion of five additional leucine residues and one serine. 相似文献
53.
E. N. Powell A. C. Morrill R. R. Bidigare 《Cellular and molecular life sciences : CMLS》1989,45(2):198-200
Vesicomyid and lucinid clams and tubeworms from Gulf of Mexico petroleum seeps, all of which bear symbiotic sulfide-oxidizing bacteria, have much lower catalase activities than shallow-water species lacking symbionts. A petroleum seep mussel bearing methane-oxidizing bacteria is unusual in having catalase activities as high as shallow-water bivalves. Unlike sulfide-dependent meiofauna from shallow-water marine sands, catalase from all petroleum seep species was inhibited by 3-amino-1,2,4-triazole.Acknowledgments. We thank S. McDonald and the crew of R/V Gyre for assistance in animal collection. This research was funded by NSF grant OCE-8219792 to EP and NSF grant OCE-83-01538 and funds from the Offshore Operators Committee to J. Brooks. We appreciate this support. 相似文献
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