Delbecq Stéphane, Auguin Daniel, Yang Yin-Shan, Löhr Frank, Arold Stefan, Schetters Theo, Précigout Eric, Gorenflot André, Roumestand Christian
DIMNP, Université Montpellier 1 et 2, CNRS, Laboratoire de Biologie Cellulaire et Moléculaire, ERT 1038, Faculté de Pharmacie BP 14491, Université de Montpellier I, 15 Avenue Charles Flahault, 34093 Montpellier Cedex 5, France.
J Mol Biol. 2008 Jan 11;375(2):409-24. doi: 10.1016/j.jmb.2007.08.019. Epub 2007 Aug 21.
Babesia divergens is the Apicomplexa agent of the bovine babesiosis in Europe: this infection leads to growth and lactation decrease, so that economical losses due to this parasite are sufficient to require the development of a vaccine. The major surface antigen of B. divergens has been described as a 37 kDa protein glycosyl phosphatidyl inositol (GPI)-anchored at the surface of the merozoite. The immuno-prophylactic potential of Bd37 has been demonstrated, and we present here the high-resolution solution structure of the 27 kDa structured core of Bd37 (Delta-Bd37) using NMR spectroscopy. A model for the whole protein has been obtained using additional small angle X-ray scattering (SAXS) data. The knowledge of the 3D structure of Bd37 allowed the precise epitope mapping of antibodies on its surface. Interestingly, the geometry of Delta-Bd37 reveals an intriguing similarity with the exocyst subunit Exo84p C-terminal region, an eukaryotic protein that has a direct implication in vesicle trafficking. This strongly suggests that Apicomplexa have developed in parallel molecular machines similar in structure and function to the ones used for endo- and exocytosis in eukaryotic cells.
这种感染会导致生长和泌乳减少,因此这种寄生虫造成的经济损失足以促使开发一种疫苗。分歧巴贝斯虫的主要表面抗原被描述为一种37 kDa的蛋白,通过糖基磷脂酰肌醇(GPI)锚定在裂殖子表面。Bd37的免疫预防潜力已得到证实,我们在此展示了使用核磁共振光谱法测定的Bd37(Delta-Bd37)27 kDa结构化核心的高分辨率溶液结构。利用额外的小角X射线散射(SAXS)数据获得了整个蛋白质的模型。Bd37三维结构的知识使得能够在其表面精确绘制抗体的表位。有趣的是,Delta-Bd37的几何结构与外排体亚基Exo84p的C末端区域有着引人注目的相似性,Exo84p是一种真核蛋白,直接参与囊泡运输。这有力地表明,顶复门已经平行地发展出了在结构和功能上与真核细胞用于内吞和外排作用的分子机器相似的分子机器。