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Heterotrimeric G-proteins, composed of , and subunits, participate in a wide range of signaling pathways in eukaryotes (Morris and Malbon, 1999). According to the typical, mammalian paradigm, in its
 

Summary: Synopsis
Heterotrimeric G-proteins, composed of , and subunits, participate in a wide range of signaling
pathways in eukaryotes (Morris and Malbon, 1999). According to the typical, mammalian paradigm, in its
inactive state, the G-protein exists as an associated heterotrimer. G-protein signaling begins with ligand
binding that results in a conformational change in a G-protein-coupled receptor (GPCR). Once activated
by the GPCR, the G separates from the associated G dimer and the freed G and G proteins can
then interact with downstream effector molecules, alone or in combination, to transduce the signal.
Subsequent to signal propagation, G re-associates with the G dimer to reform the G-protein complex.
There are several classical routes for signal propagation via heterotrimeric G-proteins that have been
categorized in mammalian systems (Marrari et al., 2007; Dupre et al., 2009). One route, which we
designate classical I, requires the presence of both subunits, and can invoke one of two distinct
mechanisms. In one mechanism, upon GPCR activation, freed G and G each interact with downstream
effectors to elicit the downstream response. In a related mechanism, G but not G interacts with
downstream effectors, but the G dimer is nevertheless required to facilitate coupling of G with the
relevant GPCR (Marrari et al., 2007). In a second route, which we designate classical II, it is solely the
G dimer that interacts with downstream effectors; in this case sequestration of G within the
heterotrimer prevents signal propagation. In addition, a few non-classical G-protein regulatory modes
have also been implicated in some systems, e.g. signaling by the intact heterotrimer in yeast (Klein et al.,
2000; Frank et al., 2005). Observations such as these lead to a fundamental question, namely, which of all
the theoretical regulatory modes of G-protein signaling are realized biologically. Our study answers this

  

Source: Albert, Réka - Departments of Biology & Physics, Pennsylvania State University

 

Collections: Biology and Medicine