Insertion and interaction of transmembrane helices, from basic principles to rational design

Resumo

Membrane proteins are an important group of macromolecules that play central roles in several vital cellular processes. Although they represent around the 30% of the genes in most genomes, the information that we have about them is far away from their biological abundance and relevance. The main goal of this thesis is to delve in our understanding of membrane protein biogenesis. We studied α-helical membrane protein segments, from basic principles to rational design using some of the more relevant biochemical techniques. This work led us to a better description of how polar residues can be inserted into the membrane, improving our understanding of the insertion process and the membrane protein topology determination. We also explored the complexity of transmembrane-transmembrane interactions and their role to fine-tune apoptotic networks. Finally, we used these interactions to computationally design transmembrane inhibitors as new possible therapeutic agents to regulate cellular death.