Verdino Petra, Westritschnig Kerstin, Valenta Rudolf, Keller Walter
Institute of Chemistry, Structural Biology Group, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
EMBO J. 2002 Oct 1;21(19):5007-16. doi: 10.1093/emboj/cdf526.
The timothy grass pollen allergen Phl p 7 assembles most of the IgE epitopes of a novel family of 2 EF-hand calcium-binding proteins and therefore represents a diagnostic marker allergen and vaccine candidate for immunotherapy. Here we report the first three-dimensional structure of a representative of the 2 EF-hand allergen family, Phl p 7, in the calcium-bound form. The protein occurs as a novel dimer assembly with unique features: in contrast to well known EF-hand proteins such as calmodulin, parvalbumin or the S100 proteins, Phl p 7 adopts an extended conformation. Two protein monomers assemble in a head-to-tail arrangement with domain-swapped EF-hand pairing. The intertwined dimer adopts a barrel-like structure with an extended hydrophobic cavity providing a ligand-binding site. Calcium binding acts as a conformational switch between an open and a closed dimeric form of Phl p 7. These findings are interesting in the context of lipid- and calcium-dependent pollen tube growth. Furthermore, the structure of Phl p 7 allows for the rational development of vaccine strategies for treatment of sensitized allergic patients.
梯牧草花粉过敏原Phl p 7组装了一个新的2个EF手型钙结合蛋白家族的大部分IgE表位,因此代表了一种诊断性标记过敏原和免疫治疗的候选疫苗。在此,我们报道了2个EF手型过敏原家族的一个代表Phl p 7处于钙结合形式时的首个三维结构。该蛋白质以一种具有独特特征的新型二聚体形式存在:与钙调蛋白、小白蛋白或S100蛋白等知名的EF手型蛋白不同,Phl p 7呈现出一种伸展构象。两个蛋白质单体以头对尾的方式组装,形成结构域交换的EF手型配对。相互缠绕的二聚体采用桶状结构,具有一个伸展的疏水腔,形成一个配体结合位点。钙结合充当Phl p 7开放和闭合二聚体形式之间的构象开关。这些发现在脂质和钙依赖性花粉管生长的背景下很有趣。此外,Phl p 7的结构有助于合理制定治疗致敏过敏患者的疫苗策略。