title: The polyprotein allergens of nematodes (NPAs) - structure at last, but still mysterious.
abstract: We are engaged in structural and functional studies of several types of lipid binding protein that are only found in nematodes. Amongst these are the nematode polyprotein allergens (NPAs) and we now report the solution structure of ABA-1A (As-NPA-A1), the most repeated unit within the NPA array of Ascaris suum, which is almost identical in amino acid sequence to that of Ascaris lumbricoides. The protein forms a slightly flattened, compact, globular fold consisting of a long central helix that participates in two flanking helical bundles. Two pockets lined with apolar amino acid sidechains are apparent, one in the carboxy-terminal region of the protein, and another smaller one in the amino-terminal region. The former appears to be the main site of fatty acid binding, and the latter may have different, though possibly overlapping, ligand binding propensities. The structure of the binding sites indicates that lipid ligands are anchored within them with their hydrophobic tails oriented towards the core of the protein and their polar headgroups bound to charged sidechains at the mouth of the pockets. The three-dimensional architectures of the amino- and carboxy-terminal halves of ABA-1A are closely similar, thereby strengthening the long-suspected idea that the repeated units of NPAs themselves originate from an ancient duplication event.
authors: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Graham Kerr Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK. malcolm.kennedy@glasgow.ac.uk
authors: Malcolm W
authors: MW
authors: Kennedy
mesh_terms: D000485:Allergens / Q000737:chemistry* / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D052179:Antigens, Plant / Q000737:chemistry / Q000235:genetics; D001665:Binding Sites; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry / Q000235:genetics; D020440:Gene Duplication; D015801:Helminth Proteins / Q000737:chemistry* / Q000235:genetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D009348:Nematoda / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011487:Protein Conformation; D017510:Protein Folding; D012177:Retinol-Binding Proteins / Q000737:chemistry / Q000235:genetics; D020080:Tandem Repeat Sequences
chemical_list: C093689:ABA-1 protein, Ascaris suum; D000485:Allergens; D052179:Antigens, Plant; D050556:Fatty Acid-Binding Proteins; D015801:Helminth Proteins; D008024:Ligands; D012177:Retinol-Binding Proteins