Structure and Function of the a Subunit

The switch function of the a-subunit of the heterotrimeric G proteins is founded on the change between an active Ga-GTP conformation and an inactive Ga-GDP conformation. In this process, interaction sites with downstream effector proteins are exposed that are not available in the inactive GDP-state. The structural difference between the two conformations was explained for the transducin, Ga t, by crystallization and structural characterization of the inactive GDP form and the active GTPyS form (Lambright et al., 1994). The structures of both forms of Ga t are shown in Fig. 5.21. 

After suggestions on an iron-sulphur protein in the 6c, complex [215], this subunit was isolated and characterised by Rieske et al. [216,218], but in a form that was not active in reconstitution. Isolation in a reconstitutively active form was pioneered by Racker et al. [219], who showed that a soluble oxidation factor was required for activity. Subsequently, Trumpower and Edwards [220] purified oxidation factor and identified it as a form of the FeS protein that is active in reconstitution. An excellent review on the structure and function of the FeS protein is available [221]. 

IsomLL, Ragsdale DS, De Jongh KS etal 1995 Structure and function of the fl2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif. Cell 83 433-442 

End, R, et al. (1993). A Biosensor Approach to Probe the Structure and Function of the P85a Subunit of the Phosphatidyl-inositol 3-kinase Complex, 7 Biol. Chem. 268 10066-10075. 

Proteolytic cleavage has proven to be an efficient tool for exploring the structure and function of the Na,K-ATPase. Exposure and protection of bonds on the surface of the cytoplasmic protrusion provides unequivocal evidence for structural changes in the a subunit accompanying E1-E2 transition in Na,K-ATPase [52]. Localization of the proteolytic splits provided a shortcut to identification of residues involved in E1-E2 transition [33,53,54] and to detection of structure-function correlations [33]. Further proteolysis identifies segments at the surface of the protein and as the cytoplasmic protrusion is shaved off all ATP-dependent reactions are abolished. 

Fig. 38. Schematic representation of subunits a (A), b (B) and c (C) from E. coli Fq and their orientation in the membrane. Some conserved and essential amino acids in subunits a and c are marked. Figure source Deckers-Hebestreit and Altendorf (1996) The FoFrtype ATP synthase of bacteria Structure and function of the Fq complex. Annu Rev Microbiol 50 796.

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