Investigating the mechanism of action of TMEM16 scramblases and FATP fatty acid transporters: connecting the dots between structure and function

As membrane transporters play an essential role in cellular functions by moving endogenous compounds within and between cells, defective transport processes have been associated with numerous pathological conditions. Studying the structure and function of membrane proteins on a molecular level can answer many important biological questions and open a wide range of new possible applications. Despite their pharmacological importance, membrane proteins structure-function relationship is poorly understood as they have proven to be especially challenging targets to investigate. This thesis aimed to gain an understanding of the molecular function of two protein families – the TMEM16 family of calcium-activated phospholipid scramblases, and the fatty acid transport proteins family (FATPs). To address the structure-function relationship of these proteins, we employed single-particle cryo-electron microscopy, together with comprehensive functional studies, in order to obtain insights into their mechanism of action underlying the translocation of compounds from one side of the membrane to the other, and their regulation.