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891.
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   
892.
Membrane protein association by potential intramembrane charge pairs.   总被引:27,自引:0,他引:27  
The transmembrane domain of the alpha chain of the T-cell receptor is responsible both for its assembly with the CD3 delta chain and for rapid degradation of the unassembled chain within the endoplasmic reticulum. The determinant for both assembly and degradation is located in a segment of eight residues containing two basic amino acids. We show here that placement of a single basic residue in the transmembrane domain of the Tac antigen can induce interaction with the CD3 chain, through its transmembrane acidic residue. This interaction is most favoured when the interacting residues are located at the same level in the membrane. The ability to induce protein-protein interaction by placing charge pairs within transmembrane domains suggests an approach to producing artificial dimers.  相似文献   
893.
J A Wu  J L Manley 《Nature》1991,352(6338):818-821
Splicing of pre-messenger RNA in eukaryotic cells occurs in a multicomponent complex termed the spliceosome, which contains small nuclear ribonucleoprotein particles (snRNPs), protein factors and substrate pre-mRNA. Assembly of the spliceosome involves the stepwise binding of snRNPs and protein factors to the pre-mRNA through a poorly understood mechanism which probably involves specific RNA-RNA, RNA-protein and protein-protein interactions. Of particular interest are the interactions between snRNPs, which are likely to be important not only for assembly of the spliceosome but also for catalysis. U1 snRNP interacts with the 5' splice site and U2 snRNP with the branch site of the pre-mRNA; both of these interactions involve Watson-Crick base pairing. But very little is known about how other factors such as the U4/U6 and U5 snRNPs reach the spliceosome and function in splicing. Here we report evidence that U6 snRNA interacts directly with U2 snRNA by a mechanism involving base-pairing, and that this interaction can be necessary for splicing of a mammalian pre-mRNA in vivo.  相似文献   
894.
Human type 1 (insulin-dependent) diabetes is a common auto-immune disease of the insulin-producing beta cells of the pancreas which is caused by both genetic and environmental factors. Several features of the genetics and immunopathology of diabetes in nonobese diabetic (NOD) mice are shared with the human disease. Of the three diabetes-susceptibility genes, Idd-1 -3 and -4 that have been mapped in mice to date, only in the case of Idd-1 is there any evidence for the identity of the gene product: allelic variation within the murine immune response I-A beta gene and its human homologue HLA-DQB1 correlates with susceptibility, implying that I-A beta is a component of Idd-1. We report here the mapping of Idd-5 to the proximal region of mouse chromosome 1. This region contains at least two candidate susceptibility genes, the interleukin-1 receptor gene and Lsh/Ity/Bcg, which encodes resistance to bacterial and parasitic infections and affects the function of macrophages.  相似文献   
895.
D A Parsell  Y Sanchez  J D Stitzel  S Lindquist 《Nature》1991,353(6341):270-273
Most eukaryotic cells produce proteins with relative molecular masses in the range of 100,000 to 110,000 after exposure to high temperatures. These proteins have been studied only in yeast and mammalian cells. In Saccharomyces cerevisiae, heat-shock protein hsp104 is vital for tolerance to heat, ethanol and other stresses. The mammalian hsp110 protein is nucleolar and redistributes with growth state, nutritional conditions and heat shock. The relationships between hsp110, hsp104 and the high molecular mass heat-shock proteins of other organisms were unknown. We report here that hsp104 is a member of the highly conserved ClpA/ClpB protein family first identified in Escherichia coli and that additional heat-inducible members of this family are present in Schizosaccharomyces pombe and in mammals. Mutagenesis of two putative nucleotide-binding sites in hsp104 indicates that both are essential for function in thermotolerance.  相似文献   
896.
P Chosson  C Lanau  J Connan  D Dessort 《Nature》1991,351(6328):640-642
Biomarkers are of great value in petroleum exploration because they provide essential information about the geological history of oils and source rocks. Steranes are of particular importance as they can be related to naturally occurring precursors. These compounds generally experience intense biodegradation, however, which alters their original distribution and obscures the information that they carry regarding oil maturity and source material. In an attempt to identify the microorganisms responsible for this degradation, we have investigated the capacity of 73 aerobic bacteria to degrade steranes present in Rozel Point (Utah) oil. Seven Gram-positive strains, belonging to a limited number of genera, were found to be active. Using Nocardia sp. SEBR 16, which caused the most extensive alteration, we have determined biodegradation rates for several isomers of steranes and methylsteranes. The preference for alteration of different isomers reflects that observed in natural environments, suggesting that the degradation intermediates could be used as indicators of the extent of the biodegradation in an oil. In addition, the microorganisms used here might be effective in biodegrading oil spills.  相似文献   
897.
898.
D J Jamieson  B Rahe  J Pringle  J D Beggs 《Nature》1991,349(6311):715-717
Five small nuclear RNAs (snRNAs) are required for nuclear pre-messenger RNA splicing: U1, U2, U4, U5 and U6. The yeast U1 and U2 snRNAs base-pair to the 5' splice site and branch-point sequences of introns respectively. The role of the U5 and U4/U6 small nuclear ribonucleoprotein particles (snRNPs) in splicing is not clear, though a catalytic role for the U6 snRNA has been proposed. Less is known about yeast splicing factors, but the availability of genetic techniques in Saccharomyces cerevisiae has led to the identification of mutants deficient in nuclear pre-mRNA splicing (prp2-prp27). Several PRP genes have now been cloned and their protein products characterized. The PRP8 protein is a component of the U5 snRNP and associates with the U4/U6 snRNAs/snRNP to form a multi-snRNP particle believed to be important for spliceosome assembly. We have isolated extragenic suppressors of the prp8-1 mutation of S. cerevisiae and present here the preliminary characterization of one of these suppressors, spp81. The predicted amino-acid sequence of the SPP81 protein shows extensive similarity to a recently identified family of proteins thought to possess ATP-dependent RNA helicase activity. The possible role of this putative helicase in nuclear pre-mRNA splicing is discussed.  相似文献   
899.
Running energetics in the pronghorn antelope   总被引:1,自引:0,他引:1  
The pronghorn antelope (Antilocapra americana) has an alleged top speed of 100 km h-1, second only to the cheetah (Acionyx jubatus) among land vertebrates, a possible response to predation in the exposed habitat of the North American prairie. Unlike cheetahs, however, pronghorn antelope are distance runners rather than sprinters, and can run 11 km in 10 min, an average speed of 65 km h-1. We measured maximum oxygen uptake in pronghorn antelope to distinguish between two potential explanations for this ability: either they have evolved a uniquely high muscular efficiency (low cost of transport) or they can supply oxygen to the muscles at unusually high levels. Because the cost of transport (energy per unit distance covered per unit body mass) varies as a predictable function of body mass among terrestrial vertebrates, we can calculate the predicted cost to maintain speeds of 65 and 100 km h-1 in an average 32-kg animal. The resulting range of predicted values, 3.2-5.1 ml O2 kg-1 s-1, far surpasses the predicted maximum aerobic capacity of a 32-kg mammal (1.5 ml O2 kg-1 s-1). We conclude that their performance is achieved by an extraordinary capacity to consume and process enough oxygen to support a predicted running speed greater than 20 ms-1 (70 km h-1), attained without unique respiratory-system structures.  相似文献   
900.
D Kitamura  J Roes  R Kühn  K Rajewsky 《Nature》1991,350(6317):423-426
Of the various classes of antibodies that B lymphocytes can produce, class M (IgM) is the first to be expressed on the membrane of the developing cells. Pre-B cells, the precursors of B-lymphocytes, produce the heavy chain of IgM (mu chain), but not light chains. Recent data suggest that pre-B cells express mu chains on the membrane together with the 'surrogate' light chains lambda 5 and V pre B (refs 2-7). This complex could control pre-B-cell differentiation, in particular the rearrangement of the light-chain genes. We have now assessed the importance of the membrane form of the mu chain in B-cell development by generating mice lacking this chain. We disrupted one of the membrane exons of the gene encoding the mu-chain constant region by gene targeting in mouse embryonic stem cells. From these cells we derived mice heterozygous or homozygous for the mutation. B-cell development in the heterozygous mice seemed to be normal, but in homozygous animals B cells were absent, their development already being arrested at the stage of pre-B-cell maturation.  相似文献   
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