Structure/function study of the CFTR (ABCC7) chloride channel

ABC转运蛋白是一个蛋白质家族，在从细菌到人类的生物体生理中扮演着许多重要的角色。它们从细胞的不同隔间或细胞外运输各种各样的分子，如糖、维生素，甚至小蛋白。这48种人类ABC蛋白主要参与免疫系统的分泌物、药物解毒和病原体识别。对细菌ABC蛋白的结构研究有助于发现其3D结构，并提供有关其工作原理的大量信息。不幸的是，对于复杂的ABC蛋白质，比如那些资助人类的蛋白质，目前的先进技术还没有发展到足以让研究人员能够可视化其精确3D结构的方式从细胞中提取。人类ABC蛋白的大部分特征和功能特性是根据预测的与细菌ABC相似的模型推导出来的。因此，目前的人类ABC蛋白模型需要通过进一步的功能和生理相关性测试来验证。这就是我们在实验室做的研究类型。 特别是，我们研究了CFTR蛋白，这是一种重要的人类ABC转运蛋白，在调节肺、胰腺、肠道和生殖道上皮细胞的盐分和水分运动中发挥着至关重要的作用。 通过分析该蛋白质的多个方面，我们的目的是获得严重缺失的运输机制的信息，使CFTR蛋白能够发挥作用，并维持呼吸系统和消化系统的完整和良好的功能。我们的发现将适用于其他相关的ABC蛋白，这些蛋白预计具有类似的功能。

ABC transporters are a family of proteins which play numerous important roles in organisms' physiology, from bacteria to humans. They transport a wide variety of molecules such as sugars, vitamins and even small proteins from different compartments of the cell or outside of cells. The 48 human ABC proteins are mostly involved in secretions, drug detoxification, and identification of pathogens by the immune system. Structural studies of bacterial ABC proteins have been instrumental in discovering their 3D structure and providing numerous information on how they work. Unfortunately, for complex ABC proteins, such as the ones fund in humans, current advanced technologies are not developed enoughto permit extraction from cells in a way which would enable researchers to visualise their precise 3D structure. Most of the characteristics and functional properties of human ABC proteins are deduced from models based on predicted similarities with bacterial ABCs. Current models of human ABC proteins thus need to be validated by further testing for their functional and physiological relevance. This is the type of research that we do in our lab. In particular, we study the CFTR protein, an important human ABC transporter which plays a crucial role in the regulation of salts and water movement across epithelial cells of the lungs, pancreas, intestine and reproductive tract. By analyzing multiple aspects of this protein our aim is to obtain critically missing information of the transport mechanism which enables the CFTR protein to function and maintain the integrity and good function of the respiratory and digestive systems. Our findings will be applicable to other related ABC proteins which are anticipated to function similarly.