Czubinski Jaroslaw, Barciszewski Jakub, Gilski Miroslaw, Szpotkowski Kamil, Debski Janusz, Lampart-Szczapa Eleonora, Jaskolski Mariusz
Department of Food Biochemistry and Analysis, Poznan University of Life Sciences, Poznan, Poland.
Center for Biocrystallographic Research, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
Acta Crystallogr D Biol Crystallogr. 2015 Feb;71(Pt 2):224-38. doi: 10.1107/S1399004714025073. Epub 2015 Jan 23.
γ-Conglutin from lupin seeds is an unusual 7S basic globulin protein. It is capable of reducing glycaemia in mammals, but the structural basis of this activity is not known. γ-Conglutin shares a high level of structural homology with glycoside hydrolase inhibitor proteins, although it lacks any kind of inhibitory activity against plant cell-wall degradation enzymes. In addition, γ-conglutin displays a less pronounced structural similarity to pepsin-like aspartic proteases, but it is proteolytically dysfunctional. Only one structural study of a legume 7S basic globulin, that isolated from soybean, has been reported to date. The quaternary assembly of soybean 7S basic globulin (Bg7S) is arranged as a cruciform-shaped tetramer comprised of two superposed dimers. Here, the crystal structure of γ-conglutin isolated from Lupinus angustifolius seeds (LangC) is presented. The polypeptide chain of LangC is post-translationally cleaved into α and β subunits but retains its covalent integrity owing to a disulfide bridge. The protomers of LangC undergo an intricate quaternary assembly, resulting in a ring-like hexamer with noncrystallographic D3 symmetry. The twofold-related dimers are similar to those in Bg7S but their assembly is different as a consequence of mutations in a β-strand that is involved in intermolecular β-sheet formation in γ-conglutin. Structural elucidation of γ-conglutin will help to explain its physiological role, especially in the evolutionary context, and will guide further research into the hypoglycaemic activity of this protein in humans, with potential consequences for novel antidiabetic therapies.
羽扇豆种子中的γ-伴球蛋白是一种不同寻常的7S碱性球蛋白。它能够降低哺乳动物的血糖水平，但这种活性的结构基础尚不清楚。γ-伴球蛋白与糖苷水解酶抑制蛋白具有高度的结构同源性，尽管它对植物细胞壁降解酶没有任何抑制活性。此外，γ-伴球蛋白与胃蛋白酶样天冬氨酸蛋白酶的结构相似性不太明显，但它在蛋白水解方面功能失调。迄今为止，仅报道了一项对从大豆中分离出的豆科植物7S碱性球蛋白的结构研究。大豆7S碱性球蛋白（Bg7S）的四级组装呈十字形四聚体，由两个叠加的二聚体组成。在此，展示了从窄叶羽扇豆种子中分离出的γ-伴球蛋白（LangC）的晶体结构。LangC的多肽链在翻译后被切割成α和β亚基，但由于二硫键而保持其共价完整性。LangC的原体经历复杂的四级组装，形成具有非晶体学D3对称性的环状六聚体。与二倍体相关的二聚体与Bg7S中的相似，但由于γ-伴球蛋白中参与分子间β-折叠形成的β-链发生突变，它们的组装方式不同。γ-伴球蛋白的结构解析将有助于解释其生理作用，特别是在进化背景下，并将指导对该蛋白在人类中的降血糖活性的进一步研究，这可能对新型抗糖尿病疗法产生潜在影响。
