Crystallographically Mapped Ligand Binding Differs in High and Low IgE Binding Isoforms of Birch Pollen Allergen Bet v 1

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• 作者：Stefan Kofler ; Claudia Asam ; Ulrich Eckhard ; Michael Wallner ; F¨¢tima Ferreira ; Hans Br ; stetter
• 关键词：ANS ; 1-anilino-8-naphthalene sulfonate ; BRA ; brassinolide ; DXC ; deoxycholate ; iDXC ; inner deoxycholate ; oDXC ; outer deoxycholate ; LPS ; lipopolysaccharide ; MPD ; 2-methyl-2 ; 4-pentanediol ; NDSB-256 ; non-detergent sulfobetaine 256 ; PR-10 ; pathogenesis-related
• 刊名：Journal of Molecular Biology
• 出版年：2012
• 出版时间：7 September, 2012
• 年：2012
• 卷：422
• 期：1
• 页码：109-123
• 全文大小：2888 K

文摘

The ability of pathogenesis-related proteins of family 10 to bind a broad spectrum of ligands is considered to play a key role for their physiological and pathological functions. In particular, Bet v 1, an archetypical allergen from birch pollen, is described as a highly promiscuous ligand acceptor. However, the detailed recognition mechanisms, including specificity factors discriminating binding properties of naturally occurring Bet v 1 variants, are poorly understood.

Here, we report crystal structures of Bet v 1 variants in complex with an array of ligands at a resolution of up to 1.2??. Residue 30 within the hydrophobic pocket not only discriminates in high and low IgE binding Bet v 1 isoforms but also induces a drastic change in the binding mode of the model ligand deoxycholate. Ternary crystal structure complexes of Bet v 1 with several ligands together with the fluorogenic reporter 1-anilino-8-naphthalene sulfonate explain anomalous fluorescence binding curves obtained from 1-anilino-8-naphthalene sulfonate displacement assays. The structures reveal key interaction residues such as Tyr83 and rationalize both the binding specificity and promiscuity of the so-called hydrophobic pocket in Bet v 1.

The intermolecular interactions of Bet v 1 reveal an unexpected complexity that will be indispensable to fully understand its roles within the physiological and allergenic context.