Aquaporins - Novel approaches to old problems

Sammanfattning: As all life on this planet evolves around water, it is important for our bodies to be able to regulate it. This may be done passively, but just like with water in the ocean, if we were to rely solely on passive transport (such as evaporation), the flow of water would be too slow for biological functions to uphold the homeostasis that is so important for us to survive. All organisms have thus developed specialised water channels, aquaporins (AQPs), which, much like rivers, (usually) act as rapid transporters of water across land - or our lipid-rich cellular membranes.When issues arise with AQPs, disease states such as nephrogenic diabetes insipidus, Sjögren's syndrome, and cataracts may occur. These diseases are all related to the malfunction in either the integrity or regulation of the AQP responsible, or proteins related to their regulation.In this thesis, the following proteins are studied; AQP0, AQP2, and AQP5, along with their regulatory proteins calmodulin and ezrin. In the case of AQP2, the structural impact of mutations from patients are investigated in relation to their structure and function, as well as their role in causing the disease state. The study of membrane proteins as a whole is a complicated matter, mainly due to the fact that they are situated in the cell membrane. Detergents are required to isolate them from their place in the membrane, and form in structural studies using X-ray crystallography, this can be an impediment. Detergents may cause irregularities the crystal lattice, resulting in lower resolution data. These irregularities may in some cases be possible to benefit from, if they cause continuous diffraction. We have studied the nature of this type of diffraction, what causes it, and if it can be manipulated to our advantage.