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The barber’s pole worm CAP protein superfamily - A basis for fundamental discovery and biotechnology advances

Mohandas, Namitha and Young, Neil D. and Jabbar, Abdul and Korhonen, Pasi K. and Koehler, Anson V. and Amani, Parisa and Hall, Ross S. and Sternberg, Paul W. and Jex, Aaron R. and Hofmann, Andreas and Gasser, Robin B. (2015) The barber’s pole worm CAP protein superfamily - A basis for fundamental discovery and biotechnology advances. Biotechnology Advances, 33 (8). pp. 1744-1754. ISSN 0734-9750. https://resolver.caltech.edu/CaltechAUTHORS:20150811-133012832

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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 C. 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 signaling 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.biotechadv.2015.07.003DOIArticle
http://www.sciencedirect.com/science/article/pii/S0734975015300161PublisherArticle
ORCID:
AuthorORCID
Sternberg, Paul W.0000-0002-7699-0173
Additional Information:© 2015 Elsevier. Received date: 26 May 2015; Revised date: 2 July 2015; Accepted date: 11 July 2015; Available online 31 July 2015. Research funding from the National Health and Medical Research Council and Australian Research Council is gratefully acknowledged; support from the Victorian Life Sciences Computation Initiative (VLSCI) is also acknowledged (RBG). We acknowledge the contributions of all staff at WormBase (www.wormbase.org). P.W.S. thanks the Howard Hughes Medical Institute (HHMI) and the National Institutes of Health (NIH). The authors thank Christopher Lee for some assistance with bioinformatics and the collection of some articles.
Funders:
Funding AgencyGrant Number
National Health and Medical Research Council (NHMRC)UNSPECIFIED
Australian Research CouncilUNSPECIFIED
Victorian Life Sciences Computation Initiative (VLSCI)UNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIHUNSPECIFIED
Issue or Number:8
Record Number:CaltechAUTHORS:20150811-133012832
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150811-133012832
Official Citation:Namitha Mohandas, Neil D. Young, Abdul Jabbar, Pasi K. Korhonen, Anson V. Koehler, Parisa Amani, Ross S. Hall, Paul W. Sternberg, Aaron R. Jex, Andreas Hofmann, Robin B. Gasser, The barber's pole worm CAP protein superfamily — A basis for fundamental discovery and biotechnology advances, Biotechnology Advances, Volume 33, Issue 8, December 2015, Pages 1744-1754, ISSN 0734-9750, http://dx.doi.org/10.1016/j.biotechadv.2015.07.003. (http://www.sciencedirect.com/science/article/pii/S0734975015300161)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:59425
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:11 Aug 2015 20:48
Last Modified:03 Oct 2019 08:46

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