Solution Structure of a Repeated Unit of the ABA-1 Nematode Polyprotein Allergen of Ascaris Reveals a Novel Fold and Two Discrete Lipid-Binding Sites 英文参考文献.docVIP

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Solution Structure of a Repeated Unit of the ABA-1 Nematode Polyprotein Allergen of Ascaris Reveals a Novel Fold and Two Discrete Lipid-Binding Sites 英文参考文献.doc

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Solution Structure of a Repeated Unit of the ABA-1 Nematode Polyprotein Allergen of Ascaris Reveals a Novel Fold and Two Discrete Lipid-Binding Sites 英文参考文献

SolutionStructureofaRepeatedUnitoftheABA-1 NematodePolyproteinAllergenofAscarisRevealsa NovelFoldandTwoDiscreteLipid-BindingSites NicolaA.G.Meenan1¤a,GraemeBall2¤b,KrystynaBromek3,Dusˇan Uhr?′n2,AlanCooper1,MalcolmW. Kennedy3,4*,BrianO.Smith3* 1SchoolofChemistry,UniversityofGlasgow,Glasgow,Scotland,UnitedKingdom,2EdinburghBiomolecularNMRUnit,SchoolofChemistry,UniversityofEdinburgh, Edinburgh, Scotland, United Kingdom, 3Institute of Molecular, Cell and Systems Biology, University of Glasgow, Glasgow, Scotland, United Kingdom, 4Institute of Infection,ImmunityandInflammation,UniversityofGlasgow,Glasgow,Scotland,UnitedKingdom 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 responsesininfection.Insomespeciestherepeatingunitsarediverseinaminoacidsequence,but,inascaridandfilarial nematodes, many of the units areidentical 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 repertoiretothemisunderstrictgeneticcontrol. Methodology/PrincipalFindings:ThesolutionstructureofABA-1Awasdeterminedbyproteinnuclearmagneticresonance spectroscopy.Theproteinadoptsanovelseven-helicalfoldcomprisingalongcentralhelixthatparticipatesintwohollow four-helicalbundlesoneitherside.Discretehydrophobicligand-bindingpockets