Relación estructura-función en la interacción de la región C-Terminal de la proteína GY2 con membranasimplicación en la localización de la proteína G

Abstract

The main goal of this thesis was to study the interaction between Gγ2 subunit and the plasma membrane. G proteins are heterotrimeric proteins formed by the Gγ, Gβ and Gγ subunit. Heterotrimeric G proteins are peripheral membrane proteins that frequently localize to the plasma membrane. The Gγ2 subunit is modified at cysteine of the “CAAX” box by the addition of a geranylgeranyl lipid, which is followed by the proteolytic removal of the last three residues that leaves an isoprenylated and carboxyl methylated C68 as the terminal amino acid. Here, we studied if geranylgeranylation, proteolysis and carboxyl methylation could be essential for the correct localization of Gγ2 in the plasma membrane. Moreover, we studied the importance of electrostatic interactions between the inner leaflet of the plasma membrane and the positively charged C-terminal domain of the Gγ2 subunit (amino acids R62, K64 and K65) as a second signal to reach the plasma membrane. On the other hand, membrane lipid structure and composition may also affect the interaction of the protein. Previous studies have shown that the Gγ subunit may be responsible for the Gαβγ and Gβγ membrane localization, therefore, the study of the factors involved in Gγ2 subunit-plasma membrane interaction could be important to understand the signals transmission through G proteins.