急性冠状动脉综合征（Acute Coronary Syndrome， ACS）是心血管领域最为常见的致死疾病，靶向其致病因素嘌呤能受体的药物研发也成为研究的热点，仅嘌呤能受体P2Y12拮抗剂药物氯吡格雷（Clopidogrel）一项年度销售额即可达到140亿美元。然而，氯吡格雷类药物存在个体性差异大、起效慢等问题，新P2Y受体药物的研发需求仍然非常急迫。嘌呤能受体家族是一类G蛋白偶联受体，在天然细胞中表达丰度很低。这一类蛋白拥有7次跨膜结构，在溶液环境中稳定性很差，其结构解析工作有非常大的挑战。本项目以血小板上的嘌呤能受体P2Y1和P2Y12为研究对象，将采用昆虫细胞大量表达这两种受体，获得高纯度的蛋白产物并进行结晶实验，最终解析其三维结构。我们也力争得到这两种受体与其多种配体的复合物结构，这些工作必将为研究人员进一步了解心血管疾病的发生与调控，以及后续的药物研提供结构基础。

Acute Coronary Syndrome (ACS) is the most common fatal disease among heart and cardiovascular diseases, which makes the purinergic receptors (P2Ys) the hottest drug targets in the top pharmaceutical companies. The drugs targeting purinergic receptors are of greatest value. The market value of Clopidogrel, a purinergic receptor 12 (P2Y12) antagonist, is reaching 14 Billion dollars per year. However, even though Clopidogrel significantly drop the death rate of cardiovascular diseases, there are multiple issues existing in it such as slow active rate, irreversible, and rely on the metabolism of P450 which gene is greatly different among human populations. All these issues make obtaining newer generations of P2Y drug a very urgent task. Purinergic receptors belong to the G-protein coupled receptor super family, whose expression level is generally very low in their native organisms. They all have seven transmembrane helices, and are very unstable in the aqueous solution, which makes it very challenging to solve the crystal structures of these receptors. Our research will be focused on two of the platelet purinergic receptors, P2Y1 and P2Y12. These two receptors will be over expressed in our insect cell expression system, and eventually the highly purified and highly homogeneous protein sample for crystallization trials will be achieved. We will also try to obtain the co-crystals of these receptors with different ligands. By solving the crystal structures of purinergic receptors, researchers will learn more about the basis and treatment of cardiovascular diseases and our results will shed a new light on the optimizing or designing of new purinergic receptor antagonists.