Abstract

The Rab proteins are members of the Ras superfamily of small GTPases and are important regulators of intracellular vesicular transport. Like other members of this superfamily, they are involved in a cycle of GTPase and GDP exchange activity and also in a coupled cycle of reversible attachment to and detachment from membranes. These 2 cycles form the basis for coordination of a complex group of both generic and specific protein-protein as well as protein-membrane interactions. They are being studied by structural and kinetic/spectroscopic methods. Results to be discussed include those pertaining to the process of Rab prenylation, an essential requirement for their interaction with membranes, delivery of Rab proteins to membranes and the reverse process of extraction, as well as exchange of GDP for GTP catalyzed by guanine nucleotide exchange factors (GEFs). Particular emphasis will be placed on understanding the processes involved in Rab cycling and targeting and structural and kinetic results addressing the question of GEF and GDF (GDI displacement factor) activities will be presented. An additional, related topic concerns the manner in which these processes are modified by proteins from Legionella pneumophila. These proteins affect Rab function by both covalent and non-covalent processes and understanding these effects provides insight not only into events occurring during Legionella infection but also into the fundamental physiological processes referred to above.