The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Chris P Ponting - One of the best experts on this subject based on the ideXlab platform.
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a new Sequence Motif linking lissencephaly treacher collins and oral facial digital type 1 syndromes microtubule dynamics and cell migration
Human Molecular Genetics, 2001Co-Authors: Richard D Emes, Chris P PontingAbstract:: A previously unidentified Sequence Motif has been identified in the products of genes mutated in Miller-Dieker lissencephaly, Treacher Collins, oral-facial-digital type 1 and contiguous syndrome ocular albinism with late onset sensorineural deafness syndromes. An additional homologous Motif was detected in a gene product fused to the fibroblast growth factor receptor type 1 in patients with an atypical stem cell myeloproliferative disorder. In total, over 100 eukaryotic intracellular proteins are shown to possess a LIS1 homology (LisH) Motif, including several katanin p60 subunits, muskelin, tonneau, LEUNIG, Nopp140, aimless and numerous WD repeat-containing beta-propeller proteins. It is suggested that LisH Motifs contribute to the regulation of microtubule dynamics, either by mediating dimerization, or else by binding cytoplasmic dynein heavy chain or microtubules directly. The predicted secondary structure of LisH Motifs, and their occurrence in homologues of Gbeta beta-propeller subunits, suggests that they are analogues of Ggamma subunits, and might associate with the periphery of beta-propeller domains. The finding of LisH Motifs in both treacle and Nopp140 reinforces previous observations of functional similarities between these nucleolar proteins. Uncharacterized LisH Motif-containing proteins represent candidates for other diseases associated with aberrant microtubule dynamics and defects of cell migration, nucleokinesis or chromosome segregation.
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a new Sequence Motif linking lissencephaly treacher collins and oral facial digital type 1 syndromes microtubule dynamics and cell migration
Human Molecular Genetics, 2001Co-Authors: Richard D Emes, Chris P PontingAbstract:A previously unidentified Sequence Motif has been identified in the products of genes mutated in Miller-Dieker lissencephaly, Treacher Collins, oral-facial-digital type 1 and contiguous syndrome ocular albinism with late onset sensorineural deafness syndromes. An additional homologous Motif was detected in a gene product fused to the fibroblast growth factor receptor type 1 in patients with an atypical stem cell myeloproliferative disorder. In total, over 100 eukaryotic intracellular proteins are shown to possess a LIS1 homology (LisH) Motif, including several katanin p60 subunits, muskelin, tonneau, LEUNIG, Nopp140, aimless and numerous WD repeat-containing beta-propeller proteins. It is suggested that LisH Motifs contribute to the regulation of microtubule dynamics, either by mediating dimerization, or else by binding cytoplasmic dynein heavy chain or microtubules directly. The predicted secondary structure of LisH Motifs, and their occurrence in homologues of Gbeta beta-propeller subunits, suggests that they are analogues of Ggamma subunits, and might associate with the periphery of beta-propeller domains. The finding of LisH Motifs in both treacle and Nopp140 reinforces previous observations of functional similarities between these nucleolar proteins. Uncharacterized LisH Motif-containing proteins represent candidates for other diseases associated with aberrant microtubule dynamics and defects of cell migration, nucleokinesis or chromosome segregation.
Richard D Emes - One of the best experts on this subject based on the ideXlab platform.
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a new Sequence Motif linking lissencephaly treacher collins and oral facial digital type 1 syndromes microtubule dynamics and cell migration
Human Molecular Genetics, 2001Co-Authors: Richard D Emes, Chris P PontingAbstract:: A previously unidentified Sequence Motif has been identified in the products of genes mutated in Miller-Dieker lissencephaly, Treacher Collins, oral-facial-digital type 1 and contiguous syndrome ocular albinism with late onset sensorineural deafness syndromes. An additional homologous Motif was detected in a gene product fused to the fibroblast growth factor receptor type 1 in patients with an atypical stem cell myeloproliferative disorder. In total, over 100 eukaryotic intracellular proteins are shown to possess a LIS1 homology (LisH) Motif, including several katanin p60 subunits, muskelin, tonneau, LEUNIG, Nopp140, aimless and numerous WD repeat-containing beta-propeller proteins. It is suggested that LisH Motifs contribute to the regulation of microtubule dynamics, either by mediating dimerization, or else by binding cytoplasmic dynein heavy chain or microtubules directly. The predicted secondary structure of LisH Motifs, and their occurrence in homologues of Gbeta beta-propeller subunits, suggests that they are analogues of Ggamma subunits, and might associate with the periphery of beta-propeller domains. The finding of LisH Motifs in both treacle and Nopp140 reinforces previous observations of functional similarities between these nucleolar proteins. Uncharacterized LisH Motif-containing proteins represent candidates for other diseases associated with aberrant microtubule dynamics and defects of cell migration, nucleokinesis or chromosome segregation.
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a new Sequence Motif linking lissencephaly treacher collins and oral facial digital type 1 syndromes microtubule dynamics and cell migration
Human Molecular Genetics, 2001Co-Authors: Richard D Emes, Chris P PontingAbstract:A previously unidentified Sequence Motif has been identified in the products of genes mutated in Miller-Dieker lissencephaly, Treacher Collins, oral-facial-digital type 1 and contiguous syndrome ocular albinism with late onset sensorineural deafness syndromes. An additional homologous Motif was detected in a gene product fused to the fibroblast growth factor receptor type 1 in patients with an atypical stem cell myeloproliferative disorder. In total, over 100 eukaryotic intracellular proteins are shown to possess a LIS1 homology (LisH) Motif, including several katanin p60 subunits, muskelin, tonneau, LEUNIG, Nopp140, aimless and numerous WD repeat-containing beta-propeller proteins. It is suggested that LisH Motifs contribute to the regulation of microtubule dynamics, either by mediating dimerization, or else by binding cytoplasmic dynein heavy chain or microtubules directly. The predicted secondary structure of LisH Motifs, and their occurrence in homologues of Gbeta beta-propeller subunits, suggests that they are analogues of Ggamma subunits, and might associate with the periphery of beta-propeller domains. The finding of LisH Motifs in both treacle and Nopp140 reinforces previous observations of functional similarities between these nucleolar proteins. Uncharacterized LisH Motif-containing proteins represent candidates for other diseases associated with aberrant microtubule dynamics and defects of cell migration, nucleokinesis or chromosome segregation.
T Sawai - One of the best experts on this subject based on the ideXlab platform.
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metal tetracycline h antiporter of escherichia coli encoded by transposon tn10 the structural resemblance and functional difference in the role of the duplicated Sequence Motif between hydrophobic segments 2 and 3 and segments 8 and 9
Journal of Biological Chemistry, 1993Co-Authors: Akihito Yamaguchi, Tomomi Kimura, Y Someya, T SawaiAbstract:Abstract The properties of site-directed mutants as to the putative hydrophilic loop region between hydrophobic segments 2 and 3 in the transposon Tn10-encoded metal-tetracycline/H+ antiporter (TET) were reported in our previous paper (Yamaguchi, A., Someya, Y., and Sawai, T. (1992) J. Biol. Chem. 267, 19155-19162). The loop between hydrophobic segments 8 and 9 contains a conserved Sequence Motif, GXXXXKXGEK, which is a derivative of the Sequence Motif, GXXXXRXGRR, in loop2-3. Site-directed mutagenesis studies on loop8-9 revealed that the two loops exhibit significant structural resemblance, that is, 1) when the Gly residue at the eighth position in each loop was replaced by various amino acid residues, the residual activity of the resultant mutants corresponded well to the beta-turn propensity of the substituent, 2) the Cys mutant as to the fourth position in each loop was most profoundly inactivated by N-ethylmaleimide among 10 Cys mutants as to each loop, and 3) the reactivity of a Cys residue introduced at the third position in loop8-9 with N-ethylmaleimide was lower than that in the case of the other Cys mutants, probably due to the residue being partially cryptic as to the attack of the reagent, similar to in the case of the corresponding residue in loop2-3, the latter being entirely cryptic. The Gly at the first position in loop8-9 is less important than the corresponding Gly in loop2-3, however, since the TET protein suffered a loss of activity when a bulky side chain was introduced at the first position in loop8-9 as well as in loop2-3, the structural roles of the 2 glycines are likely to be similar. These findings suggested that loop2-3 and loop8-9 may occupy similar positions in the three-dimensional structure of the TET protein. On the other hand, the two loops showed a significant functional difference; the negative charge of Asp66 and the positive charge of Arg70 in loop2-3 were essential for the transport function, but, in contrast, there was no functionally essential residue in loop8-9, indicating that loop2-3 may form an "active" leaflet in the TET protein, while loop8-9 may be a "silent" counterpart.
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metal tetracycline h antiporter of escherichia coli encoded by transposon tn10 the role of a conserved Sequence Motif gxxxxrxgrr in a putative cytoplasmic loop between helices 2 and 3
Journal of Biological Chemistry, 1992Co-Authors: Akihito Yamaguchi, Y Someya, T SawaiAbstract:Abstract The region including the conserved Ser65-Asp66 dipeptide in the tetracycline/H+ antiporter (TET) encoded by transposon Tn10 is thought to play a gating role (Yamaguchi, A., Ono, N., Akasaka, T., Noumi, T., and Sawai, T. (1990) J. Biol. Chem. 265, 15525-15530). The dipeptide is in putative interhelix loop2-3, which also includes the conserved Sequence Motif, GXXXXRXGRR, found in all TET proteins and sugar/H+ symporters. Through the combination of localized random and site-directed mutagenesis, each residue in loop2-3 was replaced. Among 10 residues in putative loop2-3, the important residues, of which substitution resulted in significant reduction or complete loss of the transport activity, were Gly62, Asp66, Gly69, and Arg70. The defect in the transport activity of the Gly62 and Gly69 substitution mutants corresponded to the steric hindrance by the substituents as to the putative beta-turn structure of the peptide backbone containing these glycines. Of 3 conserved Arg residues, the replacement of only Arg70 caused complete loss of the activity except for replacement with Lys, indicating the importance of a positive charge at this position, which is similar to the essentiality of a negative charge at Asp66. A "charge-neutralizing" intra-loop salt bridge between Asp66 and Arg70 was not likely because the double mutant in which Asp66 and Arg70 were replaced with asparagine and leucine, respectively, showed no transport activity. A triple mutant with only one positive charge at Arg70 in this loop showed about half the wild-type activity, indicating that the polycationic nature of the loop was not critical for the activity. Cys mutants as to the unessential residues in the loop were modifiable with N-ethylmaleimide, except for the Met64----Cys and Arg71----Cys mutants; however, the modification of only the Ser65----Cys mutant caused significant inhibition of the transport activity, indicating that position 65 is a unique position in the structure of loop2-3.
Akihito Yamaguchi - One of the best experts on this subject based on the ideXlab platform.
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metal tetracycline h antiporter of escherichia coli encoded by transposon tn10 the structural resemblance and functional difference in the role of the duplicated Sequence Motif between hydrophobic segments 2 and 3 and segments 8 and 9
Journal of Biological Chemistry, 1993Co-Authors: Akihito Yamaguchi, Tomomi Kimura, Y Someya, T SawaiAbstract:Abstract The properties of site-directed mutants as to the putative hydrophilic loop region between hydrophobic segments 2 and 3 in the transposon Tn10-encoded metal-tetracycline/H+ antiporter (TET) were reported in our previous paper (Yamaguchi, A., Someya, Y., and Sawai, T. (1992) J. Biol. Chem. 267, 19155-19162). The loop between hydrophobic segments 8 and 9 contains a conserved Sequence Motif, GXXXXKXGEK, which is a derivative of the Sequence Motif, GXXXXRXGRR, in loop2-3. Site-directed mutagenesis studies on loop8-9 revealed that the two loops exhibit significant structural resemblance, that is, 1) when the Gly residue at the eighth position in each loop was replaced by various amino acid residues, the residual activity of the resultant mutants corresponded well to the beta-turn propensity of the substituent, 2) the Cys mutant as to the fourth position in each loop was most profoundly inactivated by N-ethylmaleimide among 10 Cys mutants as to each loop, and 3) the reactivity of a Cys residue introduced at the third position in loop8-9 with N-ethylmaleimide was lower than that in the case of the other Cys mutants, probably due to the residue being partially cryptic as to the attack of the reagent, similar to in the case of the corresponding residue in loop2-3, the latter being entirely cryptic. The Gly at the first position in loop8-9 is less important than the corresponding Gly in loop2-3, however, since the TET protein suffered a loss of activity when a bulky side chain was introduced at the first position in loop8-9 as well as in loop2-3, the structural roles of the 2 glycines are likely to be similar. These findings suggested that loop2-3 and loop8-9 may occupy similar positions in the three-dimensional structure of the TET protein. On the other hand, the two loops showed a significant functional difference; the negative charge of Asp66 and the positive charge of Arg70 in loop2-3 were essential for the transport function, but, in contrast, there was no functionally essential residue in loop8-9, indicating that loop2-3 may form an "active" leaflet in the TET protein, while loop8-9 may be a "silent" counterpart.
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metal tetracycline h antiporter of escherichia coli encoded by transposon tn10 the role of a conserved Sequence Motif gxxxxrxgrr in a putative cytoplasmic loop between helices 2 and 3
Journal of Biological Chemistry, 1992Co-Authors: Akihito Yamaguchi, Y Someya, T SawaiAbstract:Abstract The region including the conserved Ser65-Asp66 dipeptide in the tetracycline/H+ antiporter (TET) encoded by transposon Tn10 is thought to play a gating role (Yamaguchi, A., Ono, N., Akasaka, T., Noumi, T., and Sawai, T. (1990) J. Biol. Chem. 265, 15525-15530). The dipeptide is in putative interhelix loop2-3, which also includes the conserved Sequence Motif, GXXXXRXGRR, found in all TET proteins and sugar/H+ symporters. Through the combination of localized random and site-directed mutagenesis, each residue in loop2-3 was replaced. Among 10 residues in putative loop2-3, the important residues, of which substitution resulted in significant reduction or complete loss of the transport activity, were Gly62, Asp66, Gly69, and Arg70. The defect in the transport activity of the Gly62 and Gly69 substitution mutants corresponded to the steric hindrance by the substituents as to the putative beta-turn structure of the peptide backbone containing these glycines. Of 3 conserved Arg residues, the replacement of only Arg70 caused complete loss of the activity except for replacement with Lys, indicating the importance of a positive charge at this position, which is similar to the essentiality of a negative charge at Asp66. A "charge-neutralizing" intra-loop salt bridge between Asp66 and Arg70 was not likely because the double mutant in which Asp66 and Arg70 were replaced with asparagine and leucine, respectively, showed no transport activity. A triple mutant with only one positive charge at Arg70 in this loop showed about half the wild-type activity, indicating that the polycationic nature of the loop was not critical for the activity. Cys mutants as to the unessential residues in the loop were modifiable with N-ethylmaleimide, except for the Met64----Cys and Arg71----Cys mutants; however, the modification of only the Ser65----Cys mutant caused significant inhibition of the transport activity, indicating that position 65 is a unique position in the structure of loop2-3.
J Christiansen - One of the best experts on this subject based on the ideXlab platform.
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intrinsic termination of t7 rna polymerase mediated by either rna or dna
The EMBO Journal, 1996Co-Authors: L Hartvig, J ChristiansenAbstract:Intrinsic termination of T7 RNA polymerase transcription occurs at different signals in vitro. One type of signal is similar to that mediating factor-independent termination of Escherichia coli RNA polymerase, whereas the other type does not involve RNA hairpin formation. By examining the termination behaviour of T7 RNA polymerase at the E.coli rrnB operon t1 terminator, at the T7-t(phi) terminator, at the human preproparathyroid hormone gene terminator on both single- and double-stranded templates, and in the presence of GTP or ITP during transcription, we show that the termination event can be mediated by either RNA or DNA structural features. Moreover, by using co-transcriptional probing with potassium permanganate, we present evidence for the presence of transcription-induced hyperreactive thymidines on the non-template strand in the DNA-mediated event, and a putative Sequence Motif is identified. We conclude that intrinsic termination of T7 RNA polymerase transcription in vitro can be mediated either by a hairpin in the nascent RNA or by a Sequence Motif including hyperreactive thymidines in the non-template DNA strand.
