Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/69070
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Type: Journal article
Title: Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of Ascaris reveals a novel fold and two discrete
Author: Meenan, N.
Ball, G.
Bromek, K.
Uhrin, D.
Cooper, A.
Kennedy, M.
Smith, B.
Citation: PLoS Neglected Tropical Diseases, 2011; 5(4):e1040
Publisher: PLoS
Issue Date: 2011
ISSN: 1935-2727
1935-2735
Statement of
Responsibility: 
Nicola A. G. Meenan, Graeme Ball, Krystyna Bromek, Dušan Uhrín, Alan Cooper, Malcolm W. Kennedy and Brian O. Smith
Abstract: Background: Nematode polyprotein allergens (NPAs) are an unusual class of lipid-binding proteins found only in nematodes. They are synthesized as large, tandemly repetitive polyproteins that are post-translationally cleaved into multiple copies of small lipid binding proteins with virtually identical fatty acid and retinol (Vitamin A)-binding characteristics. They are probably central to transport and distribution of small hydrophobic compounds between the tissues of nematodes, and may play key roles in nutrient scavenging, immunomodulation, and IgE antibody-based responses in infection. In some species the repeating units are diverse in amino acid sequence, but, in ascarid and filarial nematodes, many of the units are identical or near-identical. ABA-1A is the most common repeating unit of the NPA of Ascaris suum, and is closely similar to that of Ascaris lumbricoides, the large intestinal roundworm of humans. Immune responses to NPAs have been associated with naturally-acquired resistance to infection in humans, and the immune repertoire to them is under strict genetic control. Methodology/Principal Findings: The solution structure of ABA-1A was determined by protein nuclear magnetic resonance spectroscopy. The protein adopts a novel seven-helical fold comprising a long central helix that participates in two hollow four-helical bundles on either side. Discrete hydrophobic ligand-binding pockets are found in the N-terminal and C-terminal bundles, and the amino acid sidechains affected by ligand (fatty acid) binding were identified. Recombinant ABA-1A contains tightly-bound ligand(s) of bacterial culture origin in one of its binding sites. Conclusions/Significance: This is the first mature, post-translationally processed, unit of a naturally-occurring tandemly-repetitive polyprotein to be structurally characterized from any source, and it belongs to a new structural class. NPAs havem no counterparts in vertebrates, so represent potential targets for drug or immunological intervention. The nature of the (as yet) unidentified bacterial ligand(s) may be pertinent to this, as will our characterization of the unusual binding sites.
Keywords: Animals; Ascaris suum; Helminth Proteins; Allergens; Magnetic Resonance Spectroscopy; Binding Sites; Protein Structure, Secondary; Protein Structure, Tertiary; Models, Molecular; Lipid Metabolism; Antigens, Plant
Rights: © 2011 Meenan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030000965
DOI: 10.1371/journal.pntd.0001040
Appears in Collections:IPAS publications
Environment Institute Leaders publications

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