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71.
72.
Retrotransposons can be used as markers because their integration creates new joints between genomic DNA and their conserved ends. To detect polymorphisms for retrotransposon insertion, marker systems generally rely on PCR amplification between these ends and some component of flanking genomic DNA. We have developed two methods, retrotransposon-microsatellite amplified polymorphism (REMAP) analysis and inter-retrotransposon amplified polymorphism (IRAP) analysis, that require neither restriction enzyme digestion nor ligation to generate the marker bands. The IRAP products are generated from two nearby retrotransposons using outward-facing primers. In REMAP, amplification between retrotransposons proximal to simple sequence repeats (microsatellites) produces the marker bands. Here, we describe protocols for the IRAP and REMAP techniques, including methods for PCR amplification with a single primer or with two primers and for agarose gel electrophoresis of the product using optimal electrophoresis buffers and conditions. This protocol can be completed in 1-2 d. 相似文献
73.
Kang X Falick AM Nelson RE Gao G Rogers K Aphasizhev R Simpson L 《The Journal of biological chemistry》2004,279(6):3893-3899
The uridine insertion/deletion editing complex, which we have termed the L-complex, is composed of at least 16 polypeptides stabilized entirely by protein-protein interactions. Three L-complex proteins contain zinc finger motifs that could be involved in these interactions. In Leishmania these proteins are labeled LC-1, LC-4, and LC-7b, and the orthologs in Trypanosoma brucei are labeled MP81, MP63, and MP42. Overexpression of TAP-tagged LC-4 in Leishmania tarentolae led to a partial localization of the protein in the L-complex together with the endogenous LC-4 protein, suggesting at least a dimeric organization. Disruption of zinc fingers 1 or 2 (ZnF-1 and ZnF-2) in the tagged LC-4 protein was performed by mutation of the two zinc-binding cysteines to glycines. Disruption of ZnF-1 led to a partial growth defect and a substantive breakdown of the L-complex, whereas disruption of ZnF-2 had no effect on cell growth and caused a partial breakdown of the L-complex. A close interaction of LC-4 with 2-4 proteins, including REL1 (RNA ligase) and LC-3, was suggested by chemical crosslinking and co-immunoprecipitation experiments. Our results suggest that both ZnF-1 and ZnF-2 in LC-4 play a role in protein-protein interactions and indicate that the LC-4 subcomplex may be required for formation or stability of the entire L-complex. 相似文献
74.
Sanishvili R Beasley S Skarina T Glesne D Joachimiak A Edwards A Savchenko A 《The Journal of biological chemistry》2004,279(40):42139-42146
The crystal structure of Escherichia coli MoaB was determined by multiwavelength anomalous diffraction phasing and refined at 1.6-A resolution. The molecule displayed a modified Rossman fold. MoaB is assembled into a hexamer composed of two trimers. The monomers have high structural similarity with two proteins, MogA and MoeA, from the molybdenum cofactor synthesis pathway in E. coli, as well as with domains of mammalian gephyrin and plant Cnx1, which are also involved in molybdopterin synthesis. Structural comparison between these proteins and the amino acid conservation patterns revealed a putative active site in MoaB. The structural analysis of this site allowed to advance several hypothesis that can be tested in further studies. 相似文献
75.
Saridakis V Yakunin A Xu X Anandakumar P Pennycooke M Gu J Cheung F Lew JM Sanishvili R Joachimiak A Arrowsmith CH Christendat D Edwards AM 《The Journal of biological chemistry》2004,279(22):23646-23653
ATP:cobalamin adenosyltransferase MMAB was recently identified as the gene responsible for a disorder of cobalamin metabolism in humans (cblB complementation group). The crystal structure of the MMAB sequence homologue from Thermoplasma acidophilum (TA1434; GenBank identification number gi|16082403) was determined to a resolution of 1.5 A. TA1434 was confirmed to be an ATP:cobalamin adenosyltransferase, which depended absolutely on divalent metal ions (Mg2+ > Mn2+ > Co2+) and only used ATP or dATP as adenosyl donors. The apparent Km of TA1434 was 110 microM (kcat = 0.23 s(-1)) for ATP, 140 microM (kcat = 0.11 s(-1)) for dATP, and 3 microM (kcat = 0.18 s(-1)) for cobalamin. TA1434 is a trimer in solution and in the crystal structure, with each subunit composed of a five-helix bundle. The location of disease-related point mutations and other residues conserved among the homologues of TA1434 suggest that the active site lies at the junctions between the subunits. Mutations in TA1434 that correspond to the disease-related mutations resulted in proteins that were inactive for ATP:cobalamin adenosyltransferase activity in vitro, confirming that these mutations define the molecular basis of the human disease. 相似文献
76.
We use a transgenic mouse model system to elucidate the regulatory regions within the human cholinergic gene locus responsible for vesicular acetylcholine transporter gene expression in vivo. In this report we characterized two transgenes for their ability to confer cholinergic-specific expression of the encoded vesicular acetylcholine transporter. An 11.2 kb transgene (named hV11.2) that spanned from about 5 kb upstream of the start of vesicular acetylcholine transporter translation down to the first choline acetyltransferase coding exon gave expression in the somatomotor neurons and a subpopulation of cholinergic neurons in the medial habenular nucleus. The second transgene (named hV6.7), a 5-prime truncated version of hV11.2 that was devoid of 4.5 kb of gene-regulatory sequences completely lacked vesicular acetylcholine transporter expression in vivo. Our data indicate that vesicular acetylcholine transporter expression in somatomotor neurons and in the medial habenular nucleus is uniquely specified within the cholinergic gene locus, and separable from cholinergic expression elsewhere. The identification of these two subdivisions of the cholinergic nervous system suggests that other cholinergic neurons in the CNS and PNS are similarly regulated by additional discrete domains within the cholinergic gene locus. 相似文献
77.
Zerjal T Xue Y Bertorelle G Wells RS Bao W Zhu S Qamar R Ayub Q Mohyuddin A Fu S Li P Yuldasheva N Ruzibakiev R Xu J Shu Q Du R Yang H Hurles ME Robinson E Gerelsaikhan T Dashnyam B Mehdi SQ Tyler-Smith C 《American journal of human genetics》2003,72(3):717-721
We have identified a Y-chromosomal lineage with several unusual features. It was found in 16 populations throughout a large region of Asia, stretching from the Pacific to the Caspian Sea, and was present at high frequency: approximately 8% of the men in this region carry it, and it thus makes up approximately 0.5% of the world total. The pattern of variation within the lineage suggested that it originated in Mongolia approximately 1,000 years ago. Such a rapid spread cannot have occurred by chance; it must have been a result of selection. The lineage is carried by likely male-line descendants of Genghis Khan, and we therefore propose that it has spread by a novel form of social selection resulting from their behavior. 相似文献
78.
Probabilistic scoring measures for profile-profile comparison yield more accurate short seed alignments 总被引:1,自引:0,他引:1
MOTIVATION: The development of powerful automatic methods for the comparison of protein sequences has become increasingly important. Profile-to-profile comparisons allow for the use of broader information about protein families, resulting in more sensitive and accurate comparisons of distantly related sequences. A key part in the comparison of two profiles is the method for the calculation of scores for the position matches. A number of methods based on various theoretical considerations have been proposed. We implemented several previously reported scoring functions as well as our own functions, and compared them on the basis of their ability to produce accurate short ungapped alignments of a given length. RESULTS: Our results suggest that the family of the probabilistic methods (log-odds based methods and prof_sim) may be the more appropriate choice for the generation of initial 'seeds' as the first step to produce local profile-profile alignments. The most effective scoring systems were the closely related modifications of functions previously implemented in the COMPASS and Picasso methods. 相似文献
79.
Metallochaperone Atox1 transfers copper to the NH2-terminal domain of the Wilson's disease protein and regulates its catalytic activity 总被引:4,自引:0,他引:4
Copper is essential for the growth and development of mammalian cells. The key role in the intracellular distribution of copper belongs to the recently discovered family of metallochaperones and to copper-transporting P-type ATPases. The mutations in the ATPase ATP7B, the Wilson's disease protein (WNDP), lead to intracellular accumulation of copper and severe hepatic and neurological abnormalities. Several of these mutations were shown to disrupt the protein-protein interactions between WNDP and the metallochaperone Atox1, suggesting that these interactions are important for normal copper homeostasis. To understand the functional consequences of the Atox1-WNDP interaction at the molecular level, we produced recombinant Atox1 and characterized its effects on WNDP. We demonstrate that Atox1 transfers copper to the purified amino-terminal domain of WNDP (N-WNDP) in a dose-dependent and saturable manner. A maximum of six copper atoms can be transferred to N-WNDP by the chaperone. Furthermore, the incubation of copper Atox1 with the full-length WNDP leads to the stimulation of the WNDP catalytic activity, providing strong evidence for the direct effect of Atox1 on the function of this transporter. Our data also suggest that Atox1 can regulate the copper occupancy of WNDP. The incubation with apo-Atox1 results in the removal of copper from the metalated N-WNDP and apparent down-regulation of WNDP activity. Interestingly, at least one copper atom remains tightly bound to N-WNDP even in the presence of excess apo-Atox1. We suggest that this incomplete reversibility reflects the functional non-equivalency of the metal-binding sites in WNDP and speculate about the intracellular consequences of the reversible Atox1-mediated copper transfer. 相似文献
80.
Tchilian EZ Dawes R Ramaley PA Whitworth JA Yuldasheva N Wells RS Watera C French N Gilks CF Kunachiwa W Ruzibakiev R Leetrakool N Carrington CV Ramdath DD Gotch F Stephens HA Hill AV Beverley PC 《Immunogenetics》2002,53(10-11):980-983
The CD45 antigen is essential for normal antigen receptor-mediated signalling in lymphocytes, and different patterns of splicing of CD45 are associated with distinct functions in lymphocytes. Abnormal CD45 splicing has been recognized in humans, caused by a C77G transversion in the gene encoding CD45 (PTPRC). Recently the C77G polymorphism has been associated with multiple sclerosis and increased susceptibility to HIV-1 infection. These studies suggest that the regulation of CD45 splicing may be critical for the proper function of the immune system. Because of these data we examined the frequency of the C77G allele in African and Asian populations from countries with high or low prevalence of HIV infection. Here we report that the variant CD45 C77G allele is absent in African populations. We further show that populations living in the Pamir mountains of Central Asia have a very high prevalence of the C77G variant. 相似文献