The plasma membrane separates the interior of cells from the outer environment. It allows cells to receive and transmit signals, to incorporate nutrients, to protect themselves from pathogens, to fuse with other cells. Different macromolecules build and control this entry passage to the cell interior, including proteins, various type of lipids and sugars, that require to be correctly localized in time and space at the cell surface.
My research focuses on a family of membrane proteins, called tetraspanins, that function as membrane-organizers. Tetraspanins maintain the plasma membrane integrity by interacting with each other or with other macromolecules, forming dynamic membrane domains. If tetraspanins are missing, if they are too abundant or defective, the membrane organization can be compromised and the cell functions affected, leading to diseases such as cancer. Because of their crucial role on the cell surface, tetraspanins can also be regarded in some cases as targets of medicines. By targeting a tetraspanin we modulate its organization activities, aiming at restoring the normal cell function.
The topic of this thesis is the biochemical, structural and functional characterization of tetraspanin CD9. We describe the structure of CD9 extracellular loop in complex with a melanoma patient-derived antibody and explain a possible mechanism of CD9 in normal and disease state. Finally, we show how coupling lipids at specific sites of CD9 influences the interaction with other cell-surface proteins, affecting the formation and composition of membrane domains.