Torres María, Palomares Oscar, Quiralte Joaquín, Pauli Gabrielle, Rodríguez Rosalía, Villalba Mayte
Biochemistry and Molecular Biology I Department Complutense, University of Madrid, Madrid, Spain.
Virgen del Rocío University, Hospital of Seville, Seville, Spain.
PLoS One. 2015 Jul 15;10(7):e0133066. doi: 10.1371/journal.pone.0133066. eCollection 2015.
Endo-β-1,3-glucanases are widespread enzymes with glycosyl hydrolitic activity involved in carbohydrate remodelling during the germination and pollen tube growth. Although members of this protein family with allergenic activity have been reported, their effective contribution to allergy is little known. In this work, we identified Fra e 9 as a novel allergenic β-1,3-glucanase from ash pollen. We produced the catalytic and carbohydrate-binding domains as two independent recombinant proteins and characterized them from structural, biochemical and immunological point of view in comparison to their counterparts from olive pollen. We showed that despite having significant differences in biochemical activity Fra e 9 and Ole e 9 display similar IgE-binding capacity, suggesting that β-1,3-glucanases represent an heterogeneous family that could display intrinsic allergenic capacity. Specific cDNA encoding Fra e 9 was cloned and sequenced. The full-length cDNA encoded a polypeptide chain of 461 amino acids containing a signal peptide of 29 residues, leading to a mature protein of 47760.2 Da and a pI of 8.66. An N-terminal catalytic domain and a C-terminal carbohydrate-binding module are the components of this enzyme. Despite the phylogenetic proximity to the olive pollen β-1,3-glucanase, Ole e 9, there is only a 39% identity between both sequences. The N- and C-terminal domains have been produced as independent recombinant proteins in Escherichia coli and Pichia pastoris, respectively. Although a low or null enzymatic activity has been associated to long β-1,3-glucanases, the recombinant N-terminal domain has 200-fold higher hydrolytic activity on laminarin than reported for Ole e 9. The C-terminal domain of Fra e 9, a cysteine-rich compact structure, is able to bind laminarin. Both molecules retain comparable IgE-binding capacity when assayed with allergic sera. In summary, the structural and functional comparison between these two closely phylogenetic related enzymes provides novel insights into the complexity of β-1,3-glucanases, representing a heterogeneous protein family with intrinsic allergenic capacity.
内切-β-1,3-葡聚糖酶是一类广泛存在的具有糖基水解活性的酶,参与种子萌发和花粉管生长过程中的碳水化合物重塑。尽管已经报道了该蛋白家族中具有致敏活性的成员,但其对过敏的实际作用仍鲜为人知。在这项研究中,我们鉴定出Fra e 9是一种来自白蜡树花粉的新型致敏β-1,3-葡聚糖酶。我们将催化结构域和碳水化合物结合结构域分别制备为两种独立的重组蛋白,并从结构、生化和免疫学角度对它们进行了表征,同时与来自橄榄花粉的相应结构域进行了比较。我们发现,尽管Fra e 9和Ole e 9在生化活性上存在显著差异,但它们表现出相似的IgE结合能力,这表明β-1,3-葡聚糖酶代表了一个可能具有内在致敏能力的异质性家族。我们克隆并测序了编码Fra e 9的特异性cDNA。全长cDNA编码一条由461个氨基酸组成的多肽链,其中包含一个29个残基的信号肽,产生的成熟蛋白分子量为47760.2 Da,pI为8.66。该酶由一个N端催化结构域和一个C端碳水化合物结合模块组成。尽管Fra e 9与橄榄花粉β-1,3-葡聚糖酶Ole e 9在系统发育上较为接近,但两者序列之间的同一性仅为39%。N端和C端结构域已分别在大肠杆菌和毕赤酵母中制备为独立的重组蛋白。尽管长链β-1,3-葡聚糖酶的酶活性较低或无活性,但重组N端结构域对海带多糖的水解活性比Ole e 9报道的高200倍。Fra e 9的C端结构域是一种富含半胱氨酸的紧密结构,能够结合海带多糖。用过敏血清检测时,这两种分子保留了相当的IgE结合能力。总之,这两种系统发育关系密切的酶之间的结构和功能比较为β-1,3-葡聚糖酶的复杂性提供了新的见解,β-1,3-葡聚糖酶代表了一个具有内在致敏能力的异质性蛋白家族。