The Experts below are selected from a list of 21192 Experts worldwide ranked by ideXlab platform
Lode Wyns - One of the best experts on this subject based on the ideXlab platform.
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antigen specificity and high affinity binding provided by one single loop of a camel single domain antibody
Journal of Biological Chemistry, 2001Co-Authors: Aline Desmyter, Serge Muyldermans, Klaas Decanniere, Lode WynsAbstract:Abstract Detailed knowledge on antibody-antigen recognition is scarce given the unlimited antibody specificities of which only few have been investigated at an atomic level. We report the crystal structures of an antibody fragment derived from a camel heavy chain antibody against carbonic anhydrase, free and in complex with antigen. Surprisingly, this single-domain antibody interacts with nanomolar affinity with the antigen through its third Hypervariable loop (19 amino acids long), providing a flat interacting surface of 620 A2. For the first time, a single-domain antibody is observed with its first Hypervariable loop adopting a type-1 canonical structure. The second Hypervariable loop, of unique size due to a somatic mutation, reveals a regular β-turn. The third Hypervariable loop covers the remaining Hypervariable loops and the side of the domain that normally interacts with the variable domain of the light chain. Specific amino acid substitutions and reoriented side chains reshape this side of the domain and increase its hydrophilicity. Of interest is the substitution of the conserved Trp-103 by Arg because it opens new perspectives to ‘humanize’ a camel variable domain of heavy chain of heavy chain antibody (VHH) or to ‘camelize’ a human or a mouse variable domain of heavy chain of conventional antibody (VH).
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antigen specificity and high affinity binding provided by one single loop of a camel single domain antibody
Journal of Biological Chemistry, 2001Co-Authors: Aline Desmyter, Serge Muyldermans, Klaas Decanniere, Lode WynsAbstract:Detailed knowledge on antibody-antigen recognition is scarce given the unlimited antibody specificities of which only few have been investigated at an atomic level. We report the crystal structures of an antibody fragment derived from a camel heavy chain antibody against carbonic anhydrase, free and in complex with antigen. Surprisingly, this single-domain antibody interacts with nanomolar affinity with the antigen through its third Hypervariable loop (19 amino acids long), providing a flat interacting surface of 620 A(2). For the first time, a single-domain antibody is observed with its first Hypervariable loop adopting a type-1 canonical structure. The second Hypervariable loop, of unique size due to a somatic mutation, reveals a regular beta-turn. The third Hypervariable loop covers the remaining Hypervariable loops and the side of the domain that normally interacts with the variable domain of the light chain. Specific amino acid substitutions and reoriented side chains reshape this side of the domain and increase its hydrophilicity. Of interest is the substitution of the conserved Trp-103 by Arg because it opens new perspectives to 'humanize' a camel variable domain of heavy chain of heavy chain antibody (VHH) or to 'camelize' a human or a mouse variable domain of heavy chain of conventional antibody (VH).
Aline Desmyter - One of the best experts on this subject based on the ideXlab platform.
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antigen specificity and high affinity binding provided by one single loop of a camel single domain antibody
Journal of Biological Chemistry, 2001Co-Authors: Aline Desmyter, Serge Muyldermans, Klaas Decanniere, Lode WynsAbstract:Abstract Detailed knowledge on antibody-antigen recognition is scarce given the unlimited antibody specificities of which only few have been investigated at an atomic level. We report the crystal structures of an antibody fragment derived from a camel heavy chain antibody against carbonic anhydrase, free and in complex with antigen. Surprisingly, this single-domain antibody interacts with nanomolar affinity with the antigen through its third Hypervariable loop (19 amino acids long), providing a flat interacting surface of 620 A2. For the first time, a single-domain antibody is observed with its first Hypervariable loop adopting a type-1 canonical structure. The second Hypervariable loop, of unique size due to a somatic mutation, reveals a regular β-turn. The third Hypervariable loop covers the remaining Hypervariable loops and the side of the domain that normally interacts with the variable domain of the light chain. Specific amino acid substitutions and reoriented side chains reshape this side of the domain and increase its hydrophilicity. Of interest is the substitution of the conserved Trp-103 by Arg because it opens new perspectives to ‘humanize’ a camel variable domain of heavy chain of heavy chain antibody (VHH) or to ‘camelize’ a human or a mouse variable domain of heavy chain of conventional antibody (VH).
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antigen specificity and high affinity binding provided by one single loop of a camel single domain antibody
Journal of Biological Chemistry, 2001Co-Authors: Aline Desmyter, Serge Muyldermans, Klaas Decanniere, Lode WynsAbstract:Detailed knowledge on antibody-antigen recognition is scarce given the unlimited antibody specificities of which only few have been investigated at an atomic level. We report the crystal structures of an antibody fragment derived from a camel heavy chain antibody against carbonic anhydrase, free and in complex with antigen. Surprisingly, this single-domain antibody interacts with nanomolar affinity with the antigen through its third Hypervariable loop (19 amino acids long), providing a flat interacting surface of 620 A(2). For the first time, a single-domain antibody is observed with its first Hypervariable loop adopting a type-1 canonical structure. The second Hypervariable loop, of unique size due to a somatic mutation, reveals a regular beta-turn. The third Hypervariable loop covers the remaining Hypervariable loops and the side of the domain that normally interacts with the variable domain of the light chain. Specific amino acid substitutions and reoriented side chains reshape this side of the domain and increase its hydrophilicity. Of interest is the substitution of the conserved Trp-103 by Arg because it opens new perspectives to 'humanize' a camel variable domain of heavy chain of heavy chain antibody (VHH) or to 'camelize' a human or a mouse variable domain of heavy chain of conventional antibody (VH).
Shunji Mishiro - One of the best experts on this subject based on the ideXlab platform.
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a structurally flexible and antigenically variable n terminal domain of the hepatitis c virus e2 ns1 protein implication for an escape from antibody
Virology, 1993Co-Authors: S Taniguchi, Hiroaki Okamoto, M Sakamoto, Maki Kojima, Fumio Tsuda, Takeshi Tanaka, Eisuke Munekata, Elizabeth Muchmore, David A Peterson, Shunji MishiroAbstract:Hepatitis C virus persists in most infected hosts, and causes chronic hepatitis, liver cirrhosis, and/or hepatocellular carcinoma in humans. During the infection the RNA genome of hepatitis C virus undergoes frequent missense mutations at one or two "Hypervariable" regions within a presumptive envelope gene (Okamoto et al., 1992, Virology 190, 894-899; Ogata et al., 1991, Proc. Natl. Acad. Sci. USA 88, 3392-3396). In the present study, we analyzed three cases of hepatitis C virus infection, two in chimpanzees and one in humans, for the antigenicity of peptides predicted from the Hypervariable region of viral RNA obtained during the follow-up. Our results showed a successive appearance of hepatitis C virus mutants with antigenically distinct amino acid sequence within the domain; and the amino acid replacement was associated with an alteration of predicted local secondary structure of the epitope region. Hence, the Hypervariable domain of the hepatitis C virus envelope appeared to be structurally flexible and antigenically variable, providing the virus a way to escape from host immunity.
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a structurally flexible and antigenically variable n terminal domain of the hepatitis c virus e2 ns1 protein implication for an escape from antibody
Virology, 1993Co-Authors: S Taniguchi, Hiroaki Okamoto, M Sakamoto, Maki Kojima, Fumio Tsuda, Takeshi Tanaka, Eisuke Munekata, Elizabeth Muchmore, David A Peterson, Shunji MishiroAbstract:Abstract Hepatitis C virus persists in most infected hosts, and causes chronic hepatitis, liver cirrhosis, and/or hepatocellular carcinoma in humans. During the infection the RNA genome of hepatitis C virus undergoes frequent missense mutations at one or two "Hypervariable" regions within a presumptive envelope gene (Okamoto et al., 1992, Virology 190, 894-899; Ogata et al., 1991, Proc. Natl. Acad. Sci. USA 88, 3392-3396). In the present study, we analyzed three cases of hepatitis C virus infection, two in chimpanzees and one in humans, for the antigenieity of peptides predicted from the Hypervariable region of viral RNA obtained during the follow-up. Our results showed a successive appearance of hepatitis C virus mutants with antigenically distinct amino acid sequence within the domain; and the amino acid replacement was associated with an alteration of predicted local secondary structure of the epitope region. Hence, the Hypervariable domain of the hepatitis C virus envelope appeared to be structurally flexible and antigenically variable, providing the virus a way to escape from host immunity.
Timothy D Swain - One of the best experts on this subject based on the ideXlab platform.
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revisiting the phylogeny of zoanthidea cnidaria anthozoa staggered alignment of Hypervariable sequences improves species tree inference
Molecular Phylogenetics and Evolution, 2018Co-Authors: Timothy D SwainAbstract:The recent rapid proliferation of novel taxon identification in the Zoanthidea has been accompanied by a parallel propagation of gene trees as a tool of species discovery, but not a corresponding increase in our understanding of phylogeny. This disparity is caused by the trade-off between the capabilities of automated DNA sequence alignment and data content of genes applied to phylogenetic inference in this group. Conserved genes or segments are easily aligned across the order, but produce poorly resolved trees; Hypervariable genes or segments contain the evolutionary signal necessary for resolution and robust support, but sequence alignment is daunting. Staggered alignments are a form of phylogeny-informed sequence alignment composed of a mosaic of local and universal regions that allow phylogenetic inference to be applied to all nucleotides from both Hypervariable and conserved gene segments. Comparisons between species tree phylogenies inferred from all data (staggered alignment) and Hypervariable-excluded data (standard alignment) demonstrate improved confidence and greater topological agreement with other sources of data for the complete-data tree. This novel phylogeny is the most comprehensive to date (in terms of taxa and data) and can serve as an expandable tool for evolutionary hypothesis testing in the Zoanthidea. Spanish language abstract available in Text S1. Translation by L. O. Swain, DePaul University, Chicago, Illinois, 60604, USA.
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revisiting the phylogeny of zoanthidea cnidaria anthozoa staggered alignment of Hypervariable sequences improves species tree inference
bioRxiv, 2017Co-Authors: Timothy D SwainAbstract:The recent rapid proliferation of novel taxon identification in the Zoanthidea has been accompanied by a parallel propagation of gene trees as a tool of species discovery, but not a corresponding increase in our understanding of phylogeny. This disparity is caused by the trade-off between the capabilities of automated DNA sequence alignment and data content of genes applied to phylogenetic inference in this group. Conserved genes or segments are easily aligned across the order, but produce poorly resolved trees; Hypervariable genes or segments contain the evolutionary signal necessary for resolution and robust support, but sequence alignment is daunting. Staggered alignments are a form of phylogeny-informed sequence alignment composed of a mosaic of local and universal regions that allow phylogenetic inference to be applied to all nucleotides from both Hypervariable and conserved gene segments. Comparisons between species tree phylogenies inferred from all data (staggered alignment) and Hypervariable-excluded data (standard alignment) demonstrate improved confidence and greater topological agreement with other sources of data for the complete-data tree. This novel phylogeny is the most comprehensive to date (in terms of taxa and data) and can serve as an expandable tool for evolutionary hypothesis testing in the Zoanthidea.
Fei Teng - One of the best experts on this subject based on the ideXlab platform.
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impact of dna extraction method and targeted 16s rrna Hypervariable region on oral microbiota profiling
Scientific Reports, 2018Co-Authors: Fei Teng, Sree Sankar Darveekaran Nair, Pengfei Zhu, Shi Huang, Fang YangAbstract:Amplification and sequencing of 16S amplicons are widely used for profiling the structure of oral microbiota. However, it remains not clear whether and to what degree DNA extraction and targeted 16S rRNA Hypervariable regions influence the analysis. Based on a mock community consisting of five oral bacterial species in equal abundance, we compared the 16S amplicon sequencing results on the Illumina MiSeq platform from six frequently employed DNA extraction procedures and three pairs of widely used 16S rRNA Hypervariable primers targeting different 16S rRNA regions. Technical reproducibility of selected 16S regions was also assessed. DNA extraction method exerted considerable influence on the observed bacterial diversity while Hypervariable regions had a relatively minor effect. Protocols with beads added to the enzyme-mediated DNA extraction reaction produced more accurate bacterial community structure than those without either beads or enzymes. Hypervariable regions targeting V3-V4 and V4-V5 seemed to produce more reproducible results than V1-V3. Neither sequencing batch nor change of operator affected the reproducibility of bacterial diversity profiles. Therefore, DNA extraction strategy and 16S rDNA Hypervariable regions both influenced the results of oral microbiota biodiversity profiling, thus should be carefully considered in study design and data interpretation.