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Molecular determinants archetypical to the phylum Nematoda.

Yin Y, Martin J, Abubucker S, Wang Z, Wyrwicz L, Rychlewski L, McCarter JP, Wilson RK, Mitreva M - BMC Genomics (2009)

Bottom Line: Nearly 1,600 of the multi-species families did not share homology to Pfam domains, including a total of 758 restricted to Nematoda.Features of these protein families were revealed through extrapolation of essential functions from observed RNAi phenotypes in C. elegans, bioinformatics-based functional annotations, identification of distant homology based on protein folds, and prediction of expression at accessible nematode surfaces.This study identified and characterized the molecular determinants that help in defining the phylum Nematoda, and therefore improved our understanding of nematode protein evolution and provided novel insights for the development of next generation parasite control strategies.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Genome Center, Department of Genetics, Washington University School of Medicine, St Louis, Missouri, USA. yyin@watson.wustl.edu

ABSTRACT

Background: Nematoda diverged from other animals between 600-1,200 million years ago and has become one of the most diverse animal phyla on earth. Most nematodes are free-living animals, but many are parasites of plants and animals including humans, posing major ecological and economical challenges around the world.

Results: We investigated phylum-specific molecular characteristics in Nematoda by exploring over 214,000 polypeptides from 32 nematode species including 27 parasites. Over 50,000 nematode protein families were identified based on primary sequence, including approximately 10% with members from at least three different species. Nearly 1,600 of the multi-species families did not share homology to Pfam domains, including a total of 758 restricted to Nematoda. Majority of the 462 families that were conserved among both free-living and parasitic species contained members from multiple nematode clades, yet approximately 90% of the 296 parasite-specific families originated only from a single clade. Features of these protein families were revealed through extrapolation of essential functions from observed RNAi phenotypes in C. elegans, bioinformatics-based functional annotations, identification of distant homology based on protein folds, and prediction of expression at accessible nematode surfaces. In addition, we identified a group of nematode-restricted sequence features in energy-generating electron transfer complexes as potential targets for new chemicals with minimal or no toxicity to the host.

Conclusion: This study identified and characterized the molecular determinants that help in defining the phylum Nematoda, and therefore improved our understanding of nematode protein evolution and provided novel insights for the development of next generation parasite control strategies.

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Related in: MedlinePlus

Structural simulation of a conserved domain in NF_0103_0974. The structure of a domain of 136 amino acids, conserved in all the five members of NF_0103_0974, were computationally simulated based on its distant homology to the PDB entry 1buqa. All the major components of 1buqa were preserved in this nematode domain, and the presence of a cysteine cluster might suggest a zinc-binding site.
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Figure 5: Structural simulation of a conserved domain in NF_0103_0974. The structure of a domain of 136 amino acids, conserved in all the five members of NF_0103_0974, were computationally simulated based on its distant homology to the PDB entry 1buqa. All the major components of 1buqa were preserved in this nematode domain, and the presence of a cysteine cluster might suggest a zinc-binding site.

Mentions: An example is family NF_0103_0974 with a domain of 136 amino acids conserved in all the five members. Several structure prediction methods included in Meta-BASIC, such as the homology modeling tool FFAS3 [53] and threading algorithms 3D-PSSM [54] and INUB [55], all assigned this conserved domain as a match to the PDB entry 1buqa, which was classified as the structure signature for a group of nuclear transport factor 2 (NTF2) like proteins. Further structural modeling using Modeller [56] showed that the nematode domain contained all the major components of this fold. The NTF2-like superfamily contains members with diverse functions, including enzymes such as enscytalone dehydratase, delta-5-3-ketosteroid isomerase, and limonene-1,2-epoxide hydrolase, and non-enzymatic homologues such as NTF2 [57]. Even though none of these functions could be clearly assigned to NF_0103_0974, the presence of a cysteine cluster might suggest the existence of zinc binding site in these nematode proteins (Figure 5).


Molecular determinants archetypical to the phylum Nematoda.

Yin Y, Martin J, Abubucker S, Wang Z, Wyrwicz L, Rychlewski L, McCarter JP, Wilson RK, Mitreva M - BMC Genomics (2009)

Structural simulation of a conserved domain in NF_0103_0974. The structure of a domain of 136 amino acids, conserved in all the five members of NF_0103_0974, were computationally simulated based on its distant homology to the PDB entry 1buqa. All the major components of 1buqa were preserved in this nematode domain, and the presence of a cysteine cluster might suggest a zinc-binding site.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2666764&req=5

Figure 5: Structural simulation of a conserved domain in NF_0103_0974. The structure of a domain of 136 amino acids, conserved in all the five members of NF_0103_0974, were computationally simulated based on its distant homology to the PDB entry 1buqa. All the major components of 1buqa were preserved in this nematode domain, and the presence of a cysteine cluster might suggest a zinc-binding site.
Mentions: An example is family NF_0103_0974 with a domain of 136 amino acids conserved in all the five members. Several structure prediction methods included in Meta-BASIC, such as the homology modeling tool FFAS3 [53] and threading algorithms 3D-PSSM [54] and INUB [55], all assigned this conserved domain as a match to the PDB entry 1buqa, which was classified as the structure signature for a group of nuclear transport factor 2 (NTF2) like proteins. Further structural modeling using Modeller [56] showed that the nematode domain contained all the major components of this fold. The NTF2-like superfamily contains members with diverse functions, including enzymes such as enscytalone dehydratase, delta-5-3-ketosteroid isomerase, and limonene-1,2-epoxide hydrolase, and non-enzymatic homologues such as NTF2 [57]. Even though none of these functions could be clearly assigned to NF_0103_0974, the presence of a cysteine cluster might suggest the existence of zinc binding site in these nematode proteins (Figure 5).

Bottom Line: Nearly 1,600 of the multi-species families did not share homology to Pfam domains, including a total of 758 restricted to Nematoda.Features of these protein families were revealed through extrapolation of essential functions from observed RNAi phenotypes in C. elegans, bioinformatics-based functional annotations, identification of distant homology based on protein folds, and prediction of expression at accessible nematode surfaces.This study identified and characterized the molecular determinants that help in defining the phylum Nematoda, and therefore improved our understanding of nematode protein evolution and provided novel insights for the development of next generation parasite control strategies.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Genome Center, Department of Genetics, Washington University School of Medicine, St Louis, Missouri, USA. yyin@watson.wustl.edu

ABSTRACT

Background: Nematoda diverged from other animals between 600-1,200 million years ago and has become one of the most diverse animal phyla on earth. Most nematodes are free-living animals, but many are parasites of plants and animals including humans, posing major ecological and economical challenges around the world.

Results: We investigated phylum-specific molecular characteristics in Nematoda by exploring over 214,000 polypeptides from 32 nematode species including 27 parasites. Over 50,000 nematode protein families were identified based on primary sequence, including approximately 10% with members from at least three different species. Nearly 1,600 of the multi-species families did not share homology to Pfam domains, including a total of 758 restricted to Nematoda. Majority of the 462 families that were conserved among both free-living and parasitic species contained members from multiple nematode clades, yet approximately 90% of the 296 parasite-specific families originated only from a single clade. Features of these protein families were revealed through extrapolation of essential functions from observed RNAi phenotypes in C. elegans, bioinformatics-based functional annotations, identification of distant homology based on protein folds, and prediction of expression at accessible nematode surfaces. In addition, we identified a group of nematode-restricted sequence features in energy-generating electron transfer complexes as potential targets for new chemicals with minimal or no toxicity to the host.

Conclusion: This study identified and characterized the molecular determinants that help in defining the phylum Nematoda, and therefore improved our understanding of nematode protein evolution and provided novel insights for the development of next generation parasite control strategies.

Show MeSH
Related in: MedlinePlus