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Josephine C Adams - One of the best experts on this subject based on the ideXlab platform.
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molecular phylogeny of the Kelch repeat superfamily reveals an expansion of btb Kelch proteins in animals
BMC Bioinformatics, 2003Co-Authors: Soren Prag, Josephine C AdamsAbstract:Background The Kelch Motif is an ancient and evolutionarily-widespread sequence Motif of 44–56 amino acids in length. It occurs as five to seven repeats that form a β-propeller tertiary structure. Over 28 Kelch-repeat proteins have been sequenced and functionally characterised from diverse organisms spanning from viruses, plants and fungi to mammals and it is evident from expressed sequence tag, domain and genome databases that many additional hypothetical proteins contain Kelch-repeats. In general, Kelch-repeat β-propellers are involved in protein-protein interactions, however the modest sequence identity between Kelch Motifs, the diversity of domain architectures, and the partial information on this protein family in any single species, all present difficulties to developing a coherent view of the Kelch-repeat domain and the Kelch-repeat protein superfamily. To understand the complexity of this superfamily of proteins, we have analysed by bioinformatics the complement of Kelch-repeat proteins encoded in the human genome and have made comparisons to the Kelch-repeat proteins encoded in other sequenced genomes.
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Molecular phylogeny of the Kelch-repeat superfamily reveals an expansion of BTB/Kelch proteins in animals
BMC Bioinformatics, 2003Co-Authors: Soren Prag, Josephine C AdamsAbstract:Background The Kelch Motif is an ancient and evolutionarily-widespread sequence Motif of 44–56 amino acids in length. It occurs as five to seven repeats that form a β-propeller tertiary structure. Over 28 Kelch-repeat proteins have been sequenced and functionally characterised from diverse organisms spanning from viruses, plants and fungi to mammals and it is evident from expressed sequence tag, domain and genome databases that many additional hypothetical proteins contain Kelch-repeats. In general, Kelch-repeat β-propellers are involved in protein-protein interactions, however the modest sequence identity between Kelch Motifs, the diversity of domain architectures, and the partial information on this protein family in any single species, all present difficulties to developing a coherent view of the Kelch-repeat domain and the Kelch-repeat protein superfamily. To understand the complexity of this superfamily of proteins, we have analysed by bioinformatics the complement of Kelch-repeat proteins encoded in the human genome and have made comparisons to the Kelch-repeat proteins encoded in other sequenced genomes. Results We identified 71 Kelch-repeat proteins encoded in the human genome, whereas 5 or 8 members were identified in yeasts and around 18 in C. elegans , D. melanogaster and A. gambiae . Multiple domain architectures were identified in each organism, including previously unrecognised forms. The vast majority of Kelch-repeat domains are predicted to form six-bladed β-propellers. The most prevalent domain architecture in the metazoan animal genomes studied was the BTB/Kelch domain organisation and we uncovered 3 subgroups of human BTB/Kelch proteins. Sequence analysis of the Kelch-repeat domains of the most robustly-related subgroups identified differences in β-propeller organisation that could provide direction for experimental study of protein-binding characteristics. Conclusion The Kelch-repeat superfamily constitutes a distinct and evolutionarily-widespread family of β-propeller domain-containing proteins. Expansion of the family during the evolution of multicellular animals is mainly accounted for by a major expansion of the BTB/Kelch domain architecture. BTB/Kelch proteins constitute 72 % of the Kelch-repeat superfamily of H. sapiens and form three subgroups, one of which appears the most-conserved during evolution. Distinctions in propeller blade organisation between subgroups 1 and 2 were identified that could provide new direction for biochemical and functional studies of novel Kelch-repeat proteins.
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Molecular phylogeny of the Kelch-repeat superfamily reveals an expansion of BTB/Kelch proteins in animals
BMC Bioinformatics, 2003Co-Authors: Soren Prag, Josephine C AdamsAbstract:Background The Kelch Motif is an ancient and evolutionarily-widespread sequence Motif of 44–56 amino acids in length. It occurs as five to seven repeats that form a β-propeller tertiary structure. Over 28 Kelch-repeat proteins have been sequenced and functionally characterised from diverse organisms spanning from viruses, plants and fungi to mammals and it is evident from expressed sequence tag, domain and genome databases that many additional hypothetical proteins contain Kelch-repeats. In general, Kelch-repeat β-propellers are involved in protein-protein interactions, however the modest sequence identity between Kelch Motifs, the diversity of domain architectures, and the partial information on this protein family in any single species, all present difficulties to developing a coherent view of the Kelch-repeat domain and the Kelch-repeat protein superfamily. To understand the complexity of this superfamily of proteins, we have analysed by bioinformatics the complement of Kelch-repeat proteins encoded in the human genome and have made comparisons to the Kelch-repeat proteins encoded in other sequenced genomes.
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The Kelch repeat superfamily of proteins: propellers of cell function.
Trends in Cell Biology, 2000Co-Authors: Josephine C Adams, Reed J. Kelso, Lynn CooleyAbstract:Abstract The Kelch Motif was discovered as a sixfold tandem element in the sequence of the Drosophila Kelch ORF1 protein. The repeated Kelch Motifs predict a conserved tertiary structure, a β-propeller. This module appears in many different polypeptide contexts and contains multiple potential protein–protein contact sites. Members of this growing superfamily are present throughout the cell and extracellularly and have diverse activities. In this review, we discuss current information concerning the structural organization of Kelch repeat proteins, their biological roles and the molecular basis of their action.
Paolo Vezzoni - One of the best experts on this subject based on the ideXlab platform.
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Mutations in conserved regions of the predicted RAG2 Kelch repeats block initiation of V(D)J recombination and result in primary immunodeficiencies.
Molecular and Cellular Biology, 2000Co-Authors: Carlos A. Gomez, Leon M. Ptaszek, Anna Villa, Fabio Bozzi, Cristina Sobacchi, Edward G. Brooks, Luigi D. Notarangelo, Eugenia Spanopoulou, Zhen-qiang Pan, Paolo VezzoniAbstract:The V(D)J recombination reaction is composed of multiple nucleolytic processing steps mediated by the recombination-activating proteins RAG1 and RAG2. Sequence analysis has suggested that RAG2 contains six Kelch repeat Motifs that are predicted to form a six-bladed b-propeller structure, with the second b-strand of each repeat demonstrating marked conservation both within and between Kelch repeat-containing proteins. Here we demonstrate that mutations G95R and DI273 within the predicted second b-strand of repeats 2 and 5 of RAG2 lead to immunodeficiency in patients P1 and P2. Green fluorescent protein fusions with the mutant proteins reveal appropriate localization to the nucleus. However, both mutations reduce the capacity of RAG2 to interact with RAG1 and block recombination signal cleavage, therefore implicating a defect in the early steps of the recombination reaction as the basis of the clinical phenotype. The present experiments, performed with an extensive panel of site-directed mutations within each of the six Kelch Motifs, further support the critical role of both hydrophobic and glycine-rich regions within the second b-strand for RAG1-RAG2 interaction and recombination signal recognition and cleavage. In contrast, multiple mutations within the variable-loop regions of the Kelch repeats had either mild or no effects on RAG1-RAG2 interaction and hence on the ability to mediate recombination. In all, the data demonstrate a critical role of the RAG2 Kelch repeats for V(D)J recombination and highlight the importance of the conserved elements of the Kelch Motif.
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Mutations in conserved regions of the predicted RAG2 Kelch repeats block initiation of V(D)J recombination and result in primary immunodeficiencies.
Molecular and cellular biology, 2000Co-Authors: Carlos A. Gomez, Leon M. Ptaszek, Anna Villa, Fabio Bozzi, Cristina Sobacchi, Edward G. Brooks, Luigi D. Notarangelo, Eugenia Spanopoulou, Zhen-qiang Pan, Paolo VezzoniAbstract:The V(D)J recombination reaction is composed of multiple nucleolytic processing steps mediated by the recombination-activating proteins RAG1 and RAG2. Sequence analysis has suggested that RAG2 contains six Kelch repeat Motifs that are predicted to form a six-bladed beta-propeller structure, with the second beta-strand of each repeat demonstrating marked conservation both within and between Kelch repeat-containing proteins. Here we demonstrate that mutations G95R and DeltaI273 within the predicted second beta-strand of repeats 2 and 5 of RAG2 lead to immunodeficiency in patients P1 and P2. Green fluorescent protein fusions with the mutant proteins reveal appropriate localization to the nucleus. However, both mutations reduce the capacity of RAG2 to interact with RAG1 and block recombination signal cleavage, therefore implicating a defect in the early steps of the recombination reaction as the basis of the clinical phenotype. The present experiments, performed with an extensive panel of site-directed mutations within each of the six Kelch Motifs, further support the critical role of both hydrophobic and glycine-rich regions within the second beta-strand for RAG1-RAG2 interaction and recombination signal recognition and cleavage. In contrast, multiple mutations within the variable-loop regions of the Kelch repeats had either mild or no effects on RAG1-RAG2 interaction and hence on the ability to mediate recombination. In all, the data demonstrate a critical role of the RAG2 Kelch repeats for V(D)J recombination and highlight the importance of the conserved elements of the Kelch Motif.
Xiaojin Luo - One of the best experts on this subject based on the ideXlab platform.
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A Kelch Motif‐Containing Serine/Threonine Protein Phosphatase Determines the Large Grain QTL Trait in Rice
Journal of integrative plant biology, 2012Co-Authors: Shiyong Zhang, Fan Sun, Xiaoyun Xin, Wenxiang Wang, Xi Qian, Jingshui Yang, Xiaojin LuoAbstract:A thorough understanding of the genetic basis of rice grain traits is critical for the improvement of rice (Oryza sativa L.) varieties. In this study, we generated an F₂ population by crossing the large-grain japonica cultivar CW23 with Peiai 64 (PA64), an elite indica small-grain cultivar. Using QTL analysis, 17 QTLs for five grain traits were detected on four different chromosomes. Eight of the QTLs were newly-identified in this study. In particular, qGL3-1, a newly-identified grain length QTL with the highest LOD value and largest phenotypic variation, was fine-mapped to the 17 kb region of chromosome 3. A serine/threonine protein phosphatase gene encoding a repeat domain containing two Kelch Motifs was identified as the unique candidate gene corresponding to this QTL. A comparison of PA64 and CW23 sequences revealed a single nucleotide substitution (C→A) at position 1092 in exon 10, resulting in replacement of Asp (D) in PA64 with Glu (E) in CW23 for the 364(th) amino acid. This variation is located at the D position of the conserved sequence Motif AVLDT of the Kelch repeat. Genetic analysis of a near-isogenic line (NIL) for qGL3-1 revealed that the allele qGL3-1 from CW23 has an additive or partly dominant effect, and is suitable for use in molecular marker-assisted selection.
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a Kelch Motif containing serine threonine protein phosphatase determines the large grain qtl trait in rice
Journal of Integrative Plant Biology, 2012Co-Authors: Shiyong Zhang, Fan Sun, Xiaoyun Xin, Wenxiang Wang, Xi Qian, Jingshui Yang, Xiaojin LuoAbstract:A thorough understanding of the genetic basis of rice grain traits is critical for the improvement of rice (Oryza sativa L.) varieties. In this study, we generated an F₂ population by crossing the large-grain japonica cultivar CW23 with Peiai 64 (PA64), an elite indica small-grain cultivar. Using QTL analysis, 17 QTLs for five grain traits were detected on four different chromosomes. Eight of the QTLs were newly-identified in this study. In particular, qGL3-1, a newly-identified grain length QTL with the highest LOD value and largest phenotypic variation, was fine-mapped to the 17 kb region of chromosome 3. A serine/threonine protein phosphatase gene encoding a repeat domain containing two Kelch Motifs was identified as the unique candidate gene corresponding to this QTL. A comparison of PA64 and CW23 sequences revealed a single nucleotide substitution (C→A) at position 1092 in exon 10, resulting in replacement of Asp (D) in PA64 with Glu (E) in CW23 for the 364(th) amino acid. This variation is located at the D position of the conserved sequence Motif AVLDT of the Kelch repeat. Genetic analysis of a near-isogenic line (NIL) for qGL3-1 revealed that the allele qGL3-1 from CW23 has an additive or partly dominant effect, and is suitable for use in molecular marker-assisted selection.
Carlos A. Gomez - One of the best experts on this subject based on the ideXlab platform.
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Mutations in conserved regions of the predicted RAG2 Kelch repeats block initiation of V(D)J recombination and result in primary immunodeficiencies.
Molecular and Cellular Biology, 2000Co-Authors: Carlos A. Gomez, Leon M. Ptaszek, Anna Villa, Fabio Bozzi, Cristina Sobacchi, Edward G. Brooks, Luigi D. Notarangelo, Eugenia Spanopoulou, Zhen-qiang Pan, Paolo VezzoniAbstract:The V(D)J recombination reaction is composed of multiple nucleolytic processing steps mediated by the recombination-activating proteins RAG1 and RAG2. Sequence analysis has suggested that RAG2 contains six Kelch repeat Motifs that are predicted to form a six-bladed b-propeller structure, with the second b-strand of each repeat demonstrating marked conservation both within and between Kelch repeat-containing proteins. Here we demonstrate that mutations G95R and DI273 within the predicted second b-strand of repeats 2 and 5 of RAG2 lead to immunodeficiency in patients P1 and P2. Green fluorescent protein fusions with the mutant proteins reveal appropriate localization to the nucleus. However, both mutations reduce the capacity of RAG2 to interact with RAG1 and block recombination signal cleavage, therefore implicating a defect in the early steps of the recombination reaction as the basis of the clinical phenotype. The present experiments, performed with an extensive panel of site-directed mutations within each of the six Kelch Motifs, further support the critical role of both hydrophobic and glycine-rich regions within the second b-strand for RAG1-RAG2 interaction and recombination signal recognition and cleavage. In contrast, multiple mutations within the variable-loop regions of the Kelch repeats had either mild or no effects on RAG1-RAG2 interaction and hence on the ability to mediate recombination. In all, the data demonstrate a critical role of the RAG2 Kelch repeats for V(D)J recombination and highlight the importance of the conserved elements of the Kelch Motif.
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Mutations in conserved regions of the predicted RAG2 Kelch repeats block initiation of V(D)J recombination and result in primary immunodeficiencies.
Molecular and cellular biology, 2000Co-Authors: Carlos A. Gomez, Leon M. Ptaszek, Anna Villa, Fabio Bozzi, Cristina Sobacchi, Edward G. Brooks, Luigi D. Notarangelo, Eugenia Spanopoulou, Zhen-qiang Pan, Paolo VezzoniAbstract:The V(D)J recombination reaction is composed of multiple nucleolytic processing steps mediated by the recombination-activating proteins RAG1 and RAG2. Sequence analysis has suggested that RAG2 contains six Kelch repeat Motifs that are predicted to form a six-bladed beta-propeller structure, with the second beta-strand of each repeat demonstrating marked conservation both within and between Kelch repeat-containing proteins. Here we demonstrate that mutations G95R and DeltaI273 within the predicted second beta-strand of repeats 2 and 5 of RAG2 lead to immunodeficiency in patients P1 and P2. Green fluorescent protein fusions with the mutant proteins reveal appropriate localization to the nucleus. However, both mutations reduce the capacity of RAG2 to interact with RAG1 and block recombination signal cleavage, therefore implicating a defect in the early steps of the recombination reaction as the basis of the clinical phenotype. The present experiments, performed with an extensive panel of site-directed mutations within each of the six Kelch Motifs, further support the critical role of both hydrophobic and glycine-rich regions within the second beta-strand for RAG1-RAG2 interaction and recombination signal recognition and cleavage. In contrast, multiple mutations within the variable-loop regions of the Kelch repeats had either mild or no effects on RAG1-RAG2 interaction and hence on the ability to mediate recombination. In all, the data demonstrate a critical role of the RAG2 Kelch repeats for V(D)J recombination and highlight the importance of the conserved elements of the Kelch Motif.
Shiyong Zhang - One of the best experts on this subject based on the ideXlab platform.
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A Kelch Motif‐Containing Serine/Threonine Protein Phosphatase Determines the Large Grain QTL Trait in Rice
Journal of integrative plant biology, 2012Co-Authors: Shiyong Zhang, Fan Sun, Xiaoyun Xin, Wenxiang Wang, Xi Qian, Jingshui Yang, Xiaojin LuoAbstract:A thorough understanding of the genetic basis of rice grain traits is critical for the improvement of rice (Oryza sativa L.) varieties. In this study, we generated an F₂ population by crossing the large-grain japonica cultivar CW23 with Peiai 64 (PA64), an elite indica small-grain cultivar. Using QTL analysis, 17 QTLs for five grain traits were detected on four different chromosomes. Eight of the QTLs were newly-identified in this study. In particular, qGL3-1, a newly-identified grain length QTL with the highest LOD value and largest phenotypic variation, was fine-mapped to the 17 kb region of chromosome 3. A serine/threonine protein phosphatase gene encoding a repeat domain containing two Kelch Motifs was identified as the unique candidate gene corresponding to this QTL. A comparison of PA64 and CW23 sequences revealed a single nucleotide substitution (C→A) at position 1092 in exon 10, resulting in replacement of Asp (D) in PA64 with Glu (E) in CW23 for the 364(th) amino acid. This variation is located at the D position of the conserved sequence Motif AVLDT of the Kelch repeat. Genetic analysis of a near-isogenic line (NIL) for qGL3-1 revealed that the allele qGL3-1 from CW23 has an additive or partly dominant effect, and is suitable for use in molecular marker-assisted selection.
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a Kelch Motif containing serine threonine protein phosphatase determines the large grain qtl trait in rice
Journal of Integrative Plant Biology, 2012Co-Authors: Shiyong Zhang, Fan Sun, Xiaoyun Xin, Wenxiang Wang, Xi Qian, Jingshui Yang, Xiaojin LuoAbstract:A thorough understanding of the genetic basis of rice grain traits is critical for the improvement of rice (Oryza sativa L.) varieties. In this study, we generated an F₂ population by crossing the large-grain japonica cultivar CW23 with Peiai 64 (PA64), an elite indica small-grain cultivar. Using QTL analysis, 17 QTLs for five grain traits were detected on four different chromosomes. Eight of the QTLs were newly-identified in this study. In particular, qGL3-1, a newly-identified grain length QTL with the highest LOD value and largest phenotypic variation, was fine-mapped to the 17 kb region of chromosome 3. A serine/threonine protein phosphatase gene encoding a repeat domain containing two Kelch Motifs was identified as the unique candidate gene corresponding to this QTL. A comparison of PA64 and CW23 sequences revealed a single nucleotide substitution (C→A) at position 1092 in exon 10, resulting in replacement of Asp (D) in PA64 with Glu (E) in CW23 for the 364(th) amino acid. This variation is located at the D position of the conserved sequence Motif AVLDT of the Kelch repeat. Genetic analysis of a near-isogenic line (NIL) for qGL3-1 revealed that the allele qGL3-1 from CW23 has an additive or partly dominant effect, and is suitable for use in molecular marker-assisted selection.