CRYSTALLOGRAPHIC STUDIES OF ALPHA GIARDINS FROM THE INTESTINAL PROTOZOAN, GIARDI

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 贾第虫是一种水传播的肠道病原体，会引发一种称为贾第虫病的腹泻。 这种早期分化的真核生物感染了全世界超过2.5亿人，并引起了广泛的症状，从无症状到慢性感染，再到肠道吸收不良和体重减轻。 贾第虫的生命周期在包囊阶段和滋养体阶段之间转换，包囊阶段是寄生虫首次以其防水和休眠形式被摄入，滋养体阶段是包囊被传递到胃并释放到小肠，在小肠中它附着，分裂并最终完成其生命周期，当它作为感染性包囊排出粪便时。 在贾第虫居住在小肠之后，它必须不断地迁移并重新附着在肠上皮上，这样寄生虫就不会被冲走，因为肠中的细胞不断地产生和替换。 鞭毛有助于寄生虫的运动，而腹盘，细胞骨架成分之一，有助于病原体附着在上皮上。 细胞骨架和贾第虫的毒力之间有很强的联系，因为正是细胞骨架帮助寄生虫移动并防止它被冲走。 以前的研究已经确定了称为α贾第虫的细胞骨架蛋白与贾第虫细胞骨架的关联。 α贾第丁家族由21个成员组成，可能在寄生虫从包囊转化为滋养体形式的脱囊中发挥关键作用。 目前，我们已经能够表达，纯化和结晶的第一个成员，从α-11贾第素家族，α-11贾第素。 我们对α-11贾丁的结构研究揭示了两种新的结构，α-11贾丁的载脂蛋白结构为1.1，α-11贾丁的钙结合结构为2.93，这揭示了一种以前没有报道过的新型钙结合位点。 我们希望继续我们对α贾第蛋白家族的结构研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Giardia lamblia is a water-borne, intestinal pathogen that triggers a form of diarrhea called giardiasis. This early diverging eukaryote infects over 250 million people worldwide and causes a wide range of symptoms from asymptomatic to chronic infection to intestinal malabsorption and weight loss. The life cycle of Giardia switches between the cyst stage when the parasite is first ingested in its water-resistant and dormant form and the trophozoite stage when the cysts are passed to the stomach and released to the small intestine where it attaches, divides and finally completes its life cycle when it is excreted in the feces as infective cysts. After Giardia has inhabited the small intestine, it constantly has to migrate and re-attach to the intestinal epithelium so that the parasite is not swept away since cells in the intestine are continuously being produced and replaced. The flagellum helps in the movement of the parasite while the ventral disk, one of the cytoskeletal components helps the pathogen attach to the epithelium. There is a strong connection between the cytoskeleton and Giardia virulence, since it is the cytoskeleton that helps the parasite move and prevents it from being swept away. Previous research studies have identified the association of cytoskeletal proteins called alpha giardins to the Giardia cytoskeleton. The alpha giardin family consists of 21 members that may play a pivotal role in excystation where the parasite converts from the cyst to the trophozoite form. Currently, we have been able to express, purify and crystallize the first member from the alpha giardin family, alpha-11 giardin. Our structural work on alpha-11 giardin has revealed two new structures, the apo structure of alpha-11 giardin to 1.1 ¿ and the calcium-bound structure of alpha-11 giardin to 2.93 ¿, which has revealed a new type of calcium binding site not previously reported before. We wish to continue our structural studies on the alpha giardin family of proteins.