Understanding membrane protein folding and interfaciality

Despite the bast abundance of membrane proteins encoded in the human genome, the understanding of their biosynthesis and folding is far from the knowledge we have of soluble proteins. In the present thesis the main objective is to increase our knowledge on membrane protein biogenesis and folding, from the first steps of folding within the ribosome to the native structure acquisition in the membrane. Hydrophobicity, helicity and length of the polypeptide chain have been stablished as the major determinants for alpha-helical conformation adoption within the ribosome exit tunnel. Also, a 'biological' interfacial scale for the 20 naturally occurring amino acids were determined due to the development of the Lep3G assay. This scale is important to deeply study the membrane interface contribution to the membrane protein integration since not all membrane proteins across the membrane, but some keep anchored to one layer. Concerning to the membrane packing, an exhaustive analysis of hydrophobic matching between largely different hydrophobic region in cells has been done for the first time. We confirmed that, in living cells, adaptations in both, the membrane thickness and transmembrane domain tilting, enable helix-helix packing besides length differences between both. Finally, we determined once again that the final topology acquisition is not only guided by the hydrophobicity of the transmembrane domains which compose the protein, but also by packing between transmembrane helices and the presence of specialized connecting loops