CRYSTALLOGRAPHIC STUDIES OF ALPHA GIARDINS FROM THE INTESTINAL PROTOZOAN, GIARDI

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 蓝氏贾第鞭毛虫是一种通过水传播的肠道病原体，它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球超过2.5亿人，并导致从无症状到慢性感染到肠道吸收不良和体重减轻等一系列症状。贾第鞭毛虫的生命周期在包囊阶段和滋养体阶段之间切换，包囊阶段是寄生虫首次以防水和休眠的形式被摄入，包囊通过胃并释放到小肠，在那里附着，分裂，最终完成其生命周期，当它作为感染性包囊从粪便中排泄出来。贾第鞭毛虫栖息在小肠后，它必须不断地迁移并重新附着到肠道上皮细胞上，这样寄生虫就不会被扫除，因为肠道中的细胞不断地产生和更换。鞭毛帮助寄生虫移动，而腹盘是细胞骨架的组成部分之一，帮助病原体附着在上皮细胞上。细胞骨架和贾第鞭毛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卷走。以前的研究已经确定了被称为阿尔法贾尔丁的细胞骨架蛋白与贾第鞭毛虫细胞骨架的关联。Alpha giardin家族由21个成员组成，它们可能在寄生虫从包囊转化为滋养体的激发过程中发挥关键作用。目前，我们已经能够表达、纯化和结晶出α-giardin家族的第一个成员--α-11 giardin。我们对α-11的结构研究揭示了两种新的结构，即α-11的apo结构为1.1°和α-11的钙结合结构为2.93°，这揭示了一种以前未见报道的新型钙结合部位。我们希望继续我们对α-giardin蛋白家族的结构研究，包括

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, which include