title: The barber's pole worm CAP protein superfamily--A basis for fundamental discovery and biotechnology advances.
abstract: Parasitic worm proteins that belong to the cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 (CAP) superfamily are proposed to play key roles in the infection process and the modulation of immune responses in host animals. However, there is limited information on these proteins for most socio-economically important worms. Here, we review the CAP protein superfamily of Haemonchus contortus (barber's pole worm), a highly significant parasitic roundworm (order Strongylida) of small ruminants. To do this, we mined genome and transcriptomic datasets, predicted and curated full-length amino acid sequences (n=45), undertook systematic phylogenetic analyses of these data and investigated transcription throughout the life cycle of H. contortus. We inferred functions for selected Caenorhabditis elegans orthologs (including vap-1, vap-2, scl-5 and lon-1) based on genetic networking and by integrating data and published information, and were able to infer that a subset of orthologs and their interaction partners play pivotal roles in growth and development via the insulin-like and/or the TGF-beta signalling pathways. The identification of the important and conserved growth regulator LON-1 led us to appraise the three-dimensional structure of this CAP protein by comparative modelling. This model revealed the presence of different topological moieties on the canonical fold of the CAP domain, which coincide with an overall charge separation as indicated by the electrostatic surface potential map. These observations suggest the existence of separate sites for effector binding and receptor interactions, and thus support the proposal that these worm molecules act in similar ways as venoms act as ligands for chemokine receptors or G protein-coupled receptor effectors. In conclusion, this review should guide future molecular studies of these molecules, and could support the development of novel interventions against haemonchosis.
authors.affiliation: The University of Melbourne, Pathogen Genomics and Genetics Program, Parkville, Victoria, Australia.
authors.forename: Namitha
authors.initials: N
authors.lastname: Mohandas
authors.affiliation: The University of Melbourne, Pathogen Genomics and Genetics Program, Parkville, Victoria, Australia.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Young
authors.affiliation: The University of Melbourne, Pathogen Genomics and Genetics Program, Parkville, Victoria, Australia.
authors.forename: Abdul
authors.initials: A
authors.lastname: Jabbar
authors.affiliation: The University of Melbourne, Pathogen Genomics and Genetics Program, Parkville, Victoria, Australia.
authors.forename: Pasi K
authors.initials: PK
authors.lastname: Korhonen
authors.affiliation: The University of Melbourne, Pathogen Genomics and Genetics Program, Parkville, Victoria, Australia.
authors.forename: Anson V
authors.initials: AV
authors.lastname: Koehler
authors.affiliation: Eskitis Institute, Griffith University, Brisbane, Australia.
authors.forename: Parisa
authors.initials: P
authors.lastname: Amani
authors.affiliation: The University of Melbourne, Pathogen Genomics and Genetics Program, Parkville, Victoria, Australia.
authors.forename: Ross S
authors.initials: RS
authors.lastname: Hall
authors.affiliation: California Institute of Technology, Division of Biology, Pasadena, CA, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sternberg
authors.affiliation: The University of Melbourne, Pathogen Genomics and Genetics Program, Parkville, Victoria, Australia.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Jex
authors.affiliation: Eskitis Institute, Griffith University, Brisbane, Australia. Electronic address: a.hofmann@griffith.edu.au.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hofmann
authors.affiliation: The University of Melbourne, Pathogen Genomics and Genetics Program, Parkville, Victoria, Australia. Electronic address: robinbg@unimelb.edu.au.
authors.forename: Robin B
authors.initials: RB
authors.lastname: Gasser
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D053263:Gene Regulatory Networks; D016678:Genome; D006189:Haemonchus / Q000235:genetics* / Q000472:pathogenicity; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010802:Phylogeny; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D043562:Receptors, G-Protein-Coupled; C454143:lon-1 protein, C elegans
keywords: CAP (SCP/TAPS) proteins; Genetic networking; Genome; Haemonchus contortus; Nematodes; Structure models; Transcription profiles; Transcriptome